BACKGROUND Premature ovarian insufficiency(POI)is a condition that causes secondary amenorrhea owing to ovarian hypofunction at an early stage.Early follicular depletion results in intractable infertility,thereby cons...BACKGROUND Premature ovarian insufficiency(POI)is a condition that causes secondary amenorrhea owing to ovarian hypofunction at an early stage.Early follicular depletion results in intractable infertility,thereby considerably reducing the quality of life of females.Given the continuum in weakened ovarian function,progressing from incipient ovarian failure(IOF)to transitional ovarian failure and further to POI,it is necessary to develop biomarkers for predicting POI.The oxidative stress states in IOF and POI were comprehensively evaluated via oxidative stress[diacron-reactive oxygen metabolites(d-ROMs)]test and anti-oxidant capacity[biological antioxidant potential(BAP)].METHODS Females presenting with secondary amenorrhea over 4 mo and a follicle stimulating hormone level of>40 mIU/mL were categorized into the POI group.Females presenting with a normal menstrual cycle and a follicle stimulating hormone level of>10.2 mIU/mL were categorized into the IOF group.Healthy females without ovarian hypofunction were categorized into the control group.Among females aged<40 years who visited our hospital from January 2021 to June 2022,we recruited 11 patients into both POI and IOF groups.For the potential antioxidant capacity,the relative oxidative stress index(BAP/d-ROMs×100)was calculated,and the oxidative stress defense system was comprehensively evaluated.RESULTS d-ROMs were significantly higher in the POI and IOF groups than in the control group,(478.2±58.7 U.CARR,434.5±60.6 U.CARR,and 341.1±35.1 U.CARR,respectively)(U.CARR is equivalent to 0.08 mg/dL of hydrogen peroxide).However,no significant difference was found between the POI and IOF groups.Regarding BAP,no significant difference was found between the control,IOF,and POI groups(2078.5±157.4μmol/L,2116.2±240.2μmol/L,and 2029.0±186.4μmol/L,respectively).The oxidative stress index was significantly higher in the POI and IOF groups than in the control group(23.7±3.3,20.7±3.6,and 16.5±2.1,respectively).However,no significant difference was found between the POI and IOF groups.CONCLUSION High levels of oxidative stress suggest that evaluating the oxidative stress state may be a useful indicator for the early detection of POI.展开更多
The incidence of premature ovarian insufficiency(POI)is increasing worldwide,particularly among younger women,posing a significant challenge to fertility.In addition to menopausal symptoms,POI leads to several complic...The incidence of premature ovarian insufficiency(POI)is increasing worldwide,particularly among younger women,posing a significant challenge to fertility.In addition to menopausal symptoms,POI leads to several complications that profoundly affect female reproductive function and overall health.Unfortunately,current clinical treatment strategies for this condition are limited and often yield unsatisfactory outcomes.These approaches typically involve hormone repla-cement therapy combined with psychological support.Recently,mesenchymal stem cell(MSC)therapies for POI have garnered considerable attention in global research.MSCs can restore ovarian reproductive and endocrine functions through diverse mechanisms,including controlling differentiation,promoting angiogenesis,regulating ovarian fibrosis,inhibiting apoptosis,enhancing autocrine and paracrine effects,suppressing inflammation,modulating the immune system,and genetic regulation.This editorial offers a succinct summary of the application of MSC therapy in the context of POI,providing evidence for groundbreaking medical approaches that have potential to enhance reproductive health and overall well-being for women.展开更多
BACKGROUND Premature ovarian insufficiency(POI)is characterized by an early decline in ovarian function,inducing secondary amenorrhea.While the cause of POI has not yet been identified,the function of mitochondria in ...BACKGROUND Premature ovarian insufficiency(POI)is characterized by an early decline in ovarian function,inducing secondary amenorrhea.While the cause of POI has not yet been identified,the function of mitochondria in the ovaries and the cytotoxicity associated with reactive oxygen species(ROS)have been implicated in follicle pool depletion and a decline in follicle quality.Recently developed tests have enabled easy measurement of diacron-reactive oxygen metabolites(d-ROMs)and biological antioxidant potential(BAP).The combination of these two tests is used to comprehensively assess oxidative stress in the blood.AIM To comprehensively assess the oxidative stress of d-ROMs and BAP in POI.METHODS Participants were classified into two groups:A POI group of 11 women aged<40 years examined between January 2021 and June 2022 with a history of secondary amenorrhea for at least 4 mo in our hospital and an FSH value of≥40 mIU/mL;and a control group of healthy women of the same age with normal ovarian function in our hospital.Plasma d-ROMs and BAP were measured in both these groups underwent.Differences between groups were assessed using the t-test.RESULTS The mean age and mean body mass index(BMI)were 35.8±3.0 years and 20.1±1.9 kg/m2 in the control group and 35.8±2.7 years and 19.4±2.5 kg/m2 in the POI group,respectively.The mean gravidity and parity in control and POI groups were 0.6±0.7 and 0.4±0.5 and 0.6±0.9 and 0.3±0.5,respectively.The two groups did not differ significantly in terms of mean age,BMI,gravidity,or parity.The d-ROMs level was significantly higher in the POI group than in the control group(478.2±58.7 vs 341.1±35.1 U.CARR;P<0.001);however,the BAP level did not significantly differ between the two groups(2078.5±157.4 vs 2029.0±186.4μmol/L).The oxidase stress index(d-ROMs/BAP×100)was significantly higher in the POI group than in the control group(23.7±3.3 vs 16.5±2.1;P<0.001).CONCLUSION Oxidative stress was significantly greater in the POI group than in the control group,suggesting oxidative stress as a factor that can serve as a POI biomarker.展开更多
Premature ovarian insufficiency,as a complex gynaecological disease,seriously threatens the physical and mental health of women of childbearing age.The main reasons for its pathogenesis are summarized.As a complex gyn...Premature ovarian insufficiency,as a complex gynaecological disease,seriously threatens the physical and mental health of women of childbearing age.The main reasons for its pathogenesis are summarized.As a complex gynaecological disease,premature ovarian insufficiency seriously threatens the physical and mental health of women of childbearing age.The causes of the disease mainly include genetic defects,autoimmune disorders,radiotherapy and chemotherapy,infection,surgery,adverse environmental exposures and other factors.In more than half of cases,the cause remains unclear.In the clinic,hormone replacement therapy is used mainly to relieve the symptoms of oestrogen deficiency.This article reviews the research progress on the causes and treatment of premature ovarian insufficiency in recent years.展开更多
OBJECTIVE:To analyze the serum metabolic targets of the"Zhibian(BL54)through Shuidao(ST28)"acupuncture technique in cyclophosphamide(CTX)-induced premature ovarian insufficiency(POI)model rats and to elucida...OBJECTIVE:To analyze the serum metabolic targets of the"Zhibian(BL54)through Shuidao(ST28)"acupuncture technique in cyclophosphamide(CTX)-induced premature ovarian insufficiency(POI)model rats and to elucidate the potential molecular mechanism of acupuncture in improving POI.METHODS:We used an intraperitoneal injection of CTX to establish the POI rat model(POI group)and compared serum hormone levels and ovarian histopathological changes to evaluate the effect of the Zhibian(BL54)through Shuidao(ST28)technique(ZS+POI group)on ovarian function.Then,nontargeted metabolomics was performed using rat serum by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS).RESULTS:After acupuncture intervention,the serum hormone levels and ovarian pathological morphology of POI rats were effectively improved.Moreover,UPLC-Q-TOF/MS results showed that the ZS+POI group showed a significant reversal of the levels of 6 differential metabolites.Among them,the levels of four serum metabolic markers,divanillyltetrahydrofuran ferulate,trans-ferulic acid,tryptamine,and neuraminic acid,increased significantly.Further analysis of biological effects showed that all metabolites were involved in the regulation of reproductive hormone levels and antioxidant and antiapoptotic effects.CONCLUSIONS:The"Zhibian(BL54)through Shuidao(ST28)"acupuncture method may improve the ovarian function of POI rats by regulating serum metabolite markers to exert antioxidant and antiapoptotic effects,which provides a theoretical basis for the clinical application of acupuncture in the treatment of POI.展开更多
Background:The prevalence of premature ovarian insufficiency(POI)is gradually increasing,safer and more effective treatments are urgently needed.Objective:The aim of this study was to evaluate the effects of Ningxin-Y...Background:The prevalence of premature ovarian insufficiency(POI)is gradually increasing,safer and more effective treatments are urgently needed.Objective:The aim of this study was to evaluate the effects of Ningxin-Yishen formula(NXYSF)on D-galactose-induced POI mice as well as to shed a light on its potential mechanisms.Methods:Six to eight weeks old female C57BL/6 mice were used in this study and randomly divided into six groups:control group;model group;estradiol valerate(EV)treatment group and NXYSF treatment group with graded doses(9.5,19,and 38 g·kg^(−1)/d).Both EV and NXYSF treatments were initiated at the 15th day of modeling and lasted for 28 days.Afterwards,the ovarian function was evaluated in each group by analyzing the proportion of primordial follicles as well as the serum sex hormone levels.Furthermore,network pharmacology approach was performed to elucidate the potential targets of NXYSF,which was verified through western blotting experiments finally.Results:NXYSF could significantly reverse the inefficiency of weight gain caused by POI,and promote the devel-opment of primordial follicles.In addition,it could restore the abnormal serum anti-Müllerian hormone(AMH),estradiol(E 2),luteinizing hormone(LH)and follicle-stimulating hormone(FSH).Moreover,some crucial key gene targets including TP53 were as propose to be relate with the effect of NXYSF through network pharmacology anal-ysis.Last but importantly,western blotting experiments confirmed that NXYSF could inhibit the expression of p53 protein in mouse ovaries.展开更多
Background:Premature ovarian insufficiency(POI)is a common refractory disease in gynecology,and its etiology and pathogenesis are complex.Psychological stress exerts an impact on women’s physical and mental health,an...Background:Premature ovarian insufficiency(POI)is a common refractory disease in gynecology,and its etiology and pathogenesis are complex.Psychological stress exerts an impact on women’s physical and mental health,and in turn affects the ovarian reserve function,which is one of the important etiologies and pathogenesis of POI.The compound formula Ningxin Tongyu Zishen Tang(NTZT)is composed of Chinese herbal medicines which can nourish heart and tranquilize mind,tonify kidney and supplement essence.By comparing the menstrual symptoms,traditional Chinese medicine(TCM)symptoms and the levels of serum sex hormone before and after treatment,the NTZT is clarified for its curative effect and advantages in patients with POI.Objective:The study aimed to observe the effects of NTZT on menstrual symptoms,TCM symptoms and the levels of serum sex hormone in POI patients.Methods:60 POI patients were divided into two groups,namely observation group and control group,with 30 patients in each group.The patients in both groups were treated by hormone replacement therapy(HRT).The observation and control groups received treatment with NTZT and or Liuwei Dihuang Wan(LDW),respectively.All of the patients were treated for 3 months continuously.The menstrual symptoms,TCM symptoms and the levels of serum sex hormone of the two groups were investigated before and after treatment.Results:It was found that the menstrual symptoms,TCM symptoms and the levels of serum sex hormone improved dramatically after treatment in the observation group(P<0.01).By comparison,the menstrual symptoms and the levels of serum sex hormone improved significantly(P<0.01),but no obvious improvement in TCM symptoms(P>0.05)in the control group was observed.Compared with the control group,the observation group showed significant improvement in TCM symptoms and the levels of serum sex hormone(P<0.01),but no significant difference was observed in the menstrual symptoms(P>0.05).In addition,there was no any adverse events such as gastrointestinal dysfunction and drug allergyobserved in both groups,indicating the safety of the two TCM formulas.Conclusion:The study found that NTZT could restore menstruation and improve the levels of sex hormone in patients with POI.It was also found that NTZT could eliminate the feelings of vexation,insomnia and dream-fulness,as well as tidal fever and sweating,aching pain of loins,and vaginal dryness significantly.It can be proved that NTZT is effective in treating patients with POI owing to its effects of nourishing heart and tranquil-izing mind,tonifying kidney and supplementing essence together,leading to elimination of psychological stress,which further promotes the development of the ovaries.展开更多
Objective To systematically evaluate the effectiveness and safety of acupoint stimulation therapy for treatment of premature ovarian insufficiency（POI）. Methods Computer retrieval was carried out in such databases a...Objective To systematically evaluate the effectiveness and safety of acupoint stimulation therapy for treatment of premature ovarian insufficiency（POI）. Methods Computer retrieval was carried out in such databases as Pub Med, Embase, Cochrane Library, web of science, Chinese biomedicine database（CBM）, China National Knowledge Infrastructure（CNKI）, Wan Fang and VIP in order to collect the randomized controlled trials（RCT） concerning acupoint stimulation therapy for treatment of POI. Software R 3.40 and stata 14.0 were used for Meta-analysis and network Meta-analysis, and Rev Man 5.3 was used for plotting the risk bias diagrams. Results Fortythree RCTs were included in total, involving 3046 POI patients and 18 acupoint stimulation therapies and comprehensive therapies. Metaanalysis showed：（1） The curative effects of acupoint stimulation therapy（RR=1.25, 95%CI [1.07,1.45]）, acupoint stimulation therapy＋Chinese herbal medicine（RR=1.25, 95%CI [1.18,1.32]） and acupoint stimulation therapy＋ hormone replacement therapy（HRT）（RR=1.20, 95%CI [1.12,1.29]） were all superior to that of HRT, indicating that the differences were statistically significant（Z=2.90, P=0.04; Z=7.56, P〈0.000 01; Z=4.06, P〈0.000 01）.（2） Compared with HRT, the occurrence rate of adverse effect of acupoint stimulation therapy was lower, and the safety was superior to that of HRT（RR=0.18, 95%CI [0.08,0.41]）, indicating that the differences were statistically significant（Z=4.08, P〈0.000 1）. Forty-two direct comparisons and 110 indirect comparisons were generated according to network Meta-analysis, among which, 38 comparisons were statistically significant. Network Metaanalysis results with HRT as control showed： the therapeutic measures ranking top 3 according to the curative effect sequence were catgut embedment in acupoint, moxibustion and warming-needle moxibustion, successively, and all the 3 measures were monotherapies without reflecting the advantages of comprehensive therapy. HRT ranked 17 th among the 18 included therapeutic measures. Conclusion On the basis of current evidences, acupoint stimulation therapy has a better clinical efficacy and safety for treatment of POI when compared with HRT. The acupoint stimulation therapies ranking the top 3 have more significant curative effects, but the long-term efficacy and the effect on the ovarian function still need to be further explored. In addition, the conclusion of this study still needs to be verified through a large number of RCTs with reasonable designs and appropriate methods.展开更多
Objective:To assess the reliability of the methodological quality and outcome measures of systematic reviews(SR)/meta-analysis of premature ovarian insufficiency(POI) treated with acupuncture.Methods:SR/meta-analysis ...Objective:To assess the reliability of the methodological quality and outcome measures of systematic reviews(SR)/meta-analysis of premature ovarian insufficiency(POI) treated with acupuncture.Methods:SR/meta-analysis of POI treated with acupuncture were searched on POI from the databases including PubMed,Web of Science,EMBase,the Cochran Library,Chinese biomedical literature database(SinoMed),China journal full-text database(CNKI),Wanfang data knowledge service platform(Wanfang)and VIP information Chinese periodical service platform(VIP),from inception to 1 st May 2021.Using A Measurement Tool to Assess Systematic Reviews 2(AMSTAR 2) scale and Grades of Recommendations Assessment,Development and Evaluation(GRADE) system,the methodological quality and outcome measures of the included studies were appraised.Results:Ten articles of SR/meta-analysis were included,published from 2015 to 2020.Using AMSTAR 2,5 articles of SR/meta-analysis were rated as critical low quality in methods,3 articles as low quality,and2 articles as moderate quality.The results of GRADE showed that among the 50 outcomes the quality of evidence of 22 outcomes was very low,that of 25 outcomes was low and that of 3 outcomes was moderate.Conclusion:The methodological quality and the reliability of outcome measures were not high in existing SR/meta-analysis on POI treated with acupuncture,which may affect the translation of the SR/metaanalysis findings into clinical practice.It is necessary to further strengthen the methodological quality and reporting standard of SR/meta-analysis,as well as the robustness of design and implementation of randomized controlled trials(RCTs),in order to generate high quality evidences for clinical decision-making and practice.展开更多
Objective:To analyze the effect of acupuncture versus hormone replacement therapy(HRT)for premature ovarian insufficiency(POI).Methods:China National Knowledge Infrastructure(CNKI),Wanfang Academic Journal Full-text D...Objective:To analyze the effect of acupuncture versus hormone replacement therapy(HRT)for premature ovarian insufficiency(POI).Methods:China National Knowledge Infrastructure(CNKI),Wanfang Academic Journal Full-text Database(Wanfang),Chongqing VIP Database(CQVIP),China Biology Medicine Disc(CBM),Web of Science,Cochrane Library,PubMed,and Excerpta Medica Database(EMBASE)were searched up to January 31st,2019 to identify randomized controlled trials(RCTs)evaluating the effect of acupuncture for POI.The primary outcome was the level of basal serum follicle-stimulating hormone(FSH).Secondary outcomes included serum levels of luteinizing hormone(LH),estradiol(E2)and anti-Müllerian hormone(AMH).Two authors extracted data independently and assessed the risk of bias and the methodological quality using the Cochrane's tool.Meta-analysis was conducted by RevMan version 5.3.Results:Eight eligible RCTs with a total of 496 POI patients were included in the meta-analysis.The pooled results showed that there was a significant reduction in the basal serum FSH level(MD=-5.82,95%CI:-9.76 to-1.87,I2=82%,P=0.004)and a remarkable elevation in the basal E2 level(SMD=0.93,95%CI:0.34 to 1.52,I2=88%,P=0.002)in the acupuncture group when compared with the control.Subgroup analysis showed that compared with HRT,a significant decrease in the FSH level was observed in both acupuncture alone(MD=-4.53,95%CI:-8.96 to-0.10,I2=73%,P=0.04)and acupuncture plus HRT(MD=-9.60,95%CI:-17.60 to-1.61,I2=50%,P=0.02),while a remarkable elevation of E2 was only found in acupuncture plus HRT(SMD=1.43,95%CI:1.03 to 1.82,I2=0%,P<0.00001).There was no significant difference in the LH level between acupuncture and HRT(MD=-3.16,95%CI:-9.41 to 3.10,I2=0%,P=0.32),only one trial reported AMH,and no significant difference was found between acupuncture and HRT.Conclusion:The present study indicated that acupuncture had an advantage over HRT in reducing serum FSH level and increasing serum E2 level in women with POI.However,evidence supporting the finding is limited due to the small sample size,potential methodological flaws and significant heterogeneity.Hence,this conclusion still needs to be verified by high-quality RCTs.展开更多
Premature ovarian insufficiency（POI） affects seriously physical and mental health of the patients. Studies show that acupuncture may be promising in treating POI. yet evidence is insufficient. International patient ...Premature ovarian insufficiency（POI） affects seriously physical and mental health of the patients. Studies show that acupuncture may be promising in treating POI. yet evidence is insufficient. International patient registry, one form of observational study, is designed for evaluating effectiveness and safety of acupuncture in real-world clinical settings. We will face a series of opportunities and challenges. The opportunities are as follows：（1） Interdisciplinary cooperation can improve the effect of acupuncture for POI.（2） The protocol for acupuncture to treat POI has room for improvement.（3） The patient registry study can make up the shortcomings of randomized controlled trials.（4） The patient registry study can collect real-world data and explore responses of different populations to acupuncture and can be the foundation for the successive studies. International patient registry may face technological, ethical and financial challenges, while the established International Patient Registry Platform of Acupuncture-Moxibustion（www.amreg.org：8082/v3） is actively responding to these challenges. Till now there have been more than 300 patients of POI enrolled on this platform.展开更多
Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but...Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality.The effect of chemotherapy can range from minimal effects to complete ovarian atrophy.Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility.Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist(GnRHa)during chemotherapy decreases the gonadotoxic effect of chemotherapy,thereby diminishing the chance of developing premature ovarian insufficiency(POI).At present,the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function.Notably,most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer,with a considerably small number of studies on patients with hematological malignancies.Furthermore,most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk,regardless of the hormone receptor status.In addition,studies on hematological malignancies have yielded negative results;nevertheless,thefindings must be interpreted with caution owing to numerous limitations.Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm,oocyte,and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible.In this manuscript,we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data,as well as future perspectives in thisfield that upcoming research should focus on.展开更多
Hormone therapy,assisted reproductive technology,and regenerative medicine have been used to treat infertility due to premature ovarian insufficiency(POI),with limited success.It is timely to survey the field by outli...Hormone therapy,assisted reproductive technology,and regenerative medicine have been used to treat infertility due to premature ovarian insufficiency(POI),with limited success.It is timely to survey the field by outlining the controversies and promising prospects of evolving stem cell(SC)therapy for patients with POI.We first discuss several strategies of tissue-derived SC therapy and induced/engineered SC therapy and then enumerate mechanisms,including cellular regenerability induced in reproductive tissues and paracrine effects induced by various chemokines.Next,we evaluate the potential benefits of SC-based tissue engineering in reversing ovarian aging.Finally,we discuss the clinical feasibility of SC therapy and generalized regenerative medicine for the treatment of POI.In summary,SCs and SC-derived exosomes,induced pluripotent SCs,engineered SCs,and tissue engineering could start a new chapter for fertility rehabilitation in patients with POI.Uncovering the underlying molecular mechanisms and biological efficacy could be facilitated not only by animal experiments but also by security screening and clinical trials to validate SC-based therapy for POI.展开更多
Objective:Mutations in NUP107 have been discovered in patients with premature ovarian insufficiency and may have tissue-specific effects in ovarian development.However,the role of NUP107 in human granulosa cell(GC)fun...Objective:Mutations in NUP107 have been discovered in patients with premature ovarian insufficiency and may have tissue-specific effects in ovarian development.However,the role of NUP107 in human granulosa cell(GC)function and female fertility still remains unknown.In this study,we used RNA interference to investigate how NUP107 dysfunction influences GCs and ovarian development.Methods:Immunohistochemical staining was used to detect the expression of NUP107 in ovaries.Cell counting kit-8 assay,real-time cell analysis,and flow cytometry were used to explore cell proliferation and apoptosis,and an enzyme-linked immunosorbent assay was used to assess the estrogen concentrations.Quantitative real-time reverse transcription-quantitative polymerase chain reaction and Western blot analyses were used to determine the expression of NUP107 and functional receptors.Results:Knockdown of NUP107 expression had little effect on the growth and number of GCs.Further study confirmed that knockdown of NUP107 may interfere with estrogen synthesis in GCs and their sensitivity to the regulation of follicle-stimulating hormone(FSH)by decreasing the expression of estrogen synthesis-related genes AR,CYP17A1,CYP19A1,STAR,and NR5A1.Moreover,knockdown of NUP107 decreased the expression of AMHR2,FSHR,LHR,and ESR1 in GCs,but had no effect on the expression of ESR2.Conclusions:These data revealed that NUP107 may impede follicle growth and maturation by regulating hormone synthesis,sensitivity to follicle-stimulating hormone,and expression of functional receptors in GCs,and may,therefore,interfere with female fertility.展开更多
Chemotherapy can significantly reduce follicle counts in ovarian tissues and damage ovarian stroma,causing endocrine disorder,reproductive dysfunction,and primary ovarian insufficiency(POI).Recent studies have suggest...Chemotherapy can significantly reduce follicle counts in ovarian tissues and damage ovarian stroma,causing endocrine disorder,reproductive dysfunction,and primary ovarian insufficiency(POI).Recent studies have suggested that extracellular vesicles(EVs)secreted from mesenchymal stem cells(MSCs)exert therapeutic effects in various degenerative diseases.In this study,transplantation of EVs from human induced pluripotent stem cell-derived MSCs(iPSC-MSC-EVs)resulted in significant restoration of ovarian follicle numbers,improved granulosa cell proliferation,and inhibition of apoptosis in chemotherapy-damaged granulosa cells,cultured ovaries,and in vivo ovaries in mice.Mechanistically,treatment with i PSC-MSC-EVs resulted in up-regulation of the integrinlinked kinase(ILK)-PI3K/AKT pathway,which is suppressed during chemotherapy,most likely through the transfer of regulatory microRNAs(miRNAs)targeting ILK pathway genes.This work provides a framework for the development of advanced therapeutics to ameliorate ovarian damage and POI in female chemotherapy patients.展开更多
OBJECTIVE:To investigate the efficacy of needling acupoins of Guanyuan(CV4),Sanyinjiao(SP6),Zusanli(ST36),Pishu(BL20),Shenshu(BL23),Zigong(EX-CA1)on the expression of p38 mitogen-activated protein kinase(p38MAPK)in ov...OBJECTIVE:To investigate the efficacy of needling acupoins of Guanyuan(CV4),Sanyinjiao(SP6),Zusanli(ST36),Pishu(BL20),Shenshu(BL23),Zigong(EX-CA1)on the expression of p38 mitogen-activated protein kinase(p38MAPK)in ovarian tissue in rats with premature ovarian failure induced by cyclophosphamide,and to study the underlying mechanism.METHODS:Forty specific pathogen free female Sprague-Dawley rats were randomly divided into the blank group,the model group,the acupuncture group,the Western Medicine group and the Western Medicine combined with acupuncture group.Except the blank group,the rest of the rats were given with cyclophosphamide for 14 d to establish premature ovarian failure model.No intervention was conducted in the blank group and model group;the acupuncture group was given with acupuncture daily;the Western Medicine group was given with estradiol valerate(0.09 mg/kg)by intragastrical gavage daily;the combination group was given with acupuncture combined with estradiol valerate(0.09 mg/kg)daily.Each group was intervened in continuously for 14 d.After the last treatment,the levels of estradiol(E2),follicle stimulating hormone(FSH)and luteinizing hormone(LH)were detected by enzyme-linked immunosorbent assay,then the ovarian tissue was dissected.Western blot was used to detect the expression of p38 MAPK protein.RESULTS:Compared with the blank group,E2 in the serum of rats in the model group was significantly decreased(P<0.05),FSH and LH were significantly increased(P<0.05),and the expression of p38 MAPK protein in the ovarian tissue of the rats was significantly increased(P<0.05).Compared with the model group,E2 in the serum of the acupuncture group,Western Medicine group and the combination group were significantly increased(P<0.05),FSH and LH levels were significantly decreased(P<0.05),and the expression of p38MAPK protein in the ovarian tissue of the rats was significantly decreased(P<0.05).However,there was no statistically significant difference between the Western Medicine group and the acupuncture group(P>0.05).CONCLUSIONS:Acupuncture has the same effect as estrogen in interfering POF caused by cyclophosphamide,and its mechanism may be related to inhibiting the expression of p38MAPK protein in ovarian tissue and affecting the activation of p38MAPK signaling pathway.展开更多
In India</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> the problem of infertility is growing and in the last 5 years</span><s...In India</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> the problem of infertility is growing and in the last 5 years</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> it has gone up to 20%</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">-</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">30%. This ongoing prospective clinical study brings forth a novel, innovative, effective, simple, affordable, easily performed outpatient procedure (OP) and a promising therapeutic method in rejuvenating the Ageing Ovaries and Thin Endometrium, with autologous Platelet Rich Plasma (PRP). This clinical study proves to give a better result in rejuvenating Ovary and treating the Thin Endometrium. This pilot study include</span><span style="font-family:Verdana;">d</span><span style="font-family:Verdana;"> five women (28</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">-</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">44 years) with Poor Ovarian Response (POR), Premature Ovarian Insufficiency (POI) and Perimenopause and Thirty-nine women (22</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">-</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">43</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">years.) with recurrent implantation failure due to Thin Endometrium were subjected to autologous PRP instillation under Ultrasound Guidance, and Hysteroscopic guided PRP. After PRP</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> a significant output was obtained, with improved Anti Mullerian Hormone (AMH) and Antral Follicle Count (AFC) and out of five women three women conceived by Intra Cytoplasmic Sperm Injection (ICSI). PRP injected in women with Poor Ovarian Response found successful ovarian rejuvenation within 1</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">-</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">3 months and had a 60% of pregnancy rate, PRP into the endometrium had 53.8% successful pregnancies. We have not encountered any complications.展开更多
Successful reproduction in mammals requires gamete development,fertilization,and early embryonic development.Defects in any of these processes can lead to infertility,recurrent miscarriages,and congenital defects.The ...Successful reproduction in mammals requires gamete development,fertilization,and early embryonic development.Defects in any of these processes can lead to infertility,recurrent miscarriages,and congenital defects.The clinical recognition of the genetic causes of female reproductive insufficiency using increasingly advanced genetic technologies poses a serious challenge for reproductive medicine in the 21st century.Herein,the current literature on genetic factors involved in reproductive losses was summarized.A literature search was conducted using Web of Science,MEDLINE,and PubMed databases for articles written in English on the genetic causes of women’s reproductive health disorders.Future implementation of whole-exome and wholegenome sequencing is expected to identify numerous genetic factors responsible for oocyte quality.Which will aid in increasing the likelihood of successful female reproductive function,improve the outcomes of assisted reproductive technologies,optimize treatment,and facilitate genetic diagnosis of patients.展开更多
Establishment of the primordial follicle(PF)pool is pivotal for the female reproductive lifespan;however,the mechanism of primordial folliculogenesis is poorly understood.Here,the transcription factor SP1 was shown to...Establishment of the primordial follicle(PF)pool is pivotal for the female reproductive lifespan;however,the mechanism of primordial folliculogenesis is poorly understood.Here,the transcription factor SP1 was shown to be essential for PF formation in mice.Our results showed that SP1 is present in both oocytes and somatic cells during PF formation in the ovary.Knockdown of Sp1 expression,especially in pregranulosa cells,significantly suppressed nest breakdown,oocyte apoptosis,and PF formation,suggesting that SP1 expressed by somatic cells functions in the process of primordial folliculogenesis.We further demonstrated that SP1 governs the recruitment and maintenance of Forkhead box L2-positive(FOXL2^+)pregranulosa cells using an Lgr5-EGFP-IRES-CreER^T2(Lgr5-KI)reporter mouse model and a FOXL2^+ cell-specific knockdown model.At the molecular level,SP1 functioned mainly through manipulation of NOTCH2 expression by binding directly to the promoter of the Notch2 gene.Finally,consistent with the critical role of granulosa cells in follicle survival in vitro,massive loss of oocytes in SP1 knockdown ovaries was evidenced before puberty after the ovaries were tranSP1anted under the renal capsules.Conclusively,our results reveal that SP1 controls the establishment of the ovarian reserve by regulating pregranulosa cell development in the mammalian ovary.展开更多
文摘BACKGROUND Premature ovarian insufficiency(POI)is a condition that causes secondary amenorrhea owing to ovarian hypofunction at an early stage.Early follicular depletion results in intractable infertility,thereby considerably reducing the quality of life of females.Given the continuum in weakened ovarian function,progressing from incipient ovarian failure(IOF)to transitional ovarian failure and further to POI,it is necessary to develop biomarkers for predicting POI.The oxidative stress states in IOF and POI were comprehensively evaluated via oxidative stress[diacron-reactive oxygen metabolites(d-ROMs)]test and anti-oxidant capacity[biological antioxidant potential(BAP)].METHODS Females presenting with secondary amenorrhea over 4 mo and a follicle stimulating hormone level of>40 mIU/mL were categorized into the POI group.Females presenting with a normal menstrual cycle and a follicle stimulating hormone level of>10.2 mIU/mL were categorized into the IOF group.Healthy females without ovarian hypofunction were categorized into the control group.Among females aged<40 years who visited our hospital from January 2021 to June 2022,we recruited 11 patients into both POI and IOF groups.For the potential antioxidant capacity,the relative oxidative stress index(BAP/d-ROMs×100)was calculated,and the oxidative stress defense system was comprehensively evaluated.RESULTS d-ROMs were significantly higher in the POI and IOF groups than in the control group,(478.2±58.7 U.CARR,434.5±60.6 U.CARR,and 341.1±35.1 U.CARR,respectively)(U.CARR is equivalent to 0.08 mg/dL of hydrogen peroxide).However,no significant difference was found between the POI and IOF groups.Regarding BAP,no significant difference was found between the control,IOF,and POI groups(2078.5±157.4μmol/L,2116.2±240.2μmol/L,and 2029.0±186.4μmol/L,respectively).The oxidative stress index was significantly higher in the POI and IOF groups than in the control group(23.7±3.3,20.7±3.6,and 16.5±2.1,respectively).However,no significant difference was found between the POI and IOF groups.CONCLUSION High levels of oxidative stress suggest that evaluating the oxidative stress state may be a useful indicator for the early detection of POI.
基金Supported by the Cohort Construction Project of Peking University Third Hospital,No.BYSYDL2022013Clinical Key Project of Peking University Third Hospital,No.BYSY2023049+1 种基金Special Grant for Capital Health Research and Development,No.2022-2-4097and Funding from State Key Laboratory of Female Fertility Promotion,Center for Reproductive Medicine,Department of Obstetrics and Gynecology,Peking University Third Hospital,No.BYSYSZKF2023027.
文摘The incidence of premature ovarian insufficiency(POI)is increasing worldwide,particularly among younger women,posing a significant challenge to fertility.In addition to menopausal symptoms,POI leads to several complications that profoundly affect female reproductive function and overall health.Unfortunately,current clinical treatment strategies for this condition are limited and often yield unsatisfactory outcomes.These approaches typically involve hormone repla-cement therapy combined with psychological support.Recently,mesenchymal stem cell(MSC)therapies for POI have garnered considerable attention in global research.MSCs can restore ovarian reproductive and endocrine functions through diverse mechanisms,including controlling differentiation,promoting angiogenesis,regulating ovarian fibrosis,inhibiting apoptosis,enhancing autocrine and paracrine effects,suppressing inflammation,modulating the immune system,and genetic regulation.This editorial offers a succinct summary of the application of MSC therapy in the context of POI,providing evidence for groundbreaking medical approaches that have potential to enhance reproductive health and overall well-being for women.
文摘BACKGROUND Premature ovarian insufficiency(POI)is characterized by an early decline in ovarian function,inducing secondary amenorrhea.While the cause of POI has not yet been identified,the function of mitochondria in the ovaries and the cytotoxicity associated with reactive oxygen species(ROS)have been implicated in follicle pool depletion and a decline in follicle quality.Recently developed tests have enabled easy measurement of diacron-reactive oxygen metabolites(d-ROMs)and biological antioxidant potential(BAP).The combination of these two tests is used to comprehensively assess oxidative stress in the blood.AIM To comprehensively assess the oxidative stress of d-ROMs and BAP in POI.METHODS Participants were classified into two groups:A POI group of 11 women aged<40 years examined between January 2021 and June 2022 with a history of secondary amenorrhea for at least 4 mo in our hospital and an FSH value of≥40 mIU/mL;and a control group of healthy women of the same age with normal ovarian function in our hospital.Plasma d-ROMs and BAP were measured in both these groups underwent.Differences between groups were assessed using the t-test.RESULTS The mean age and mean body mass index(BMI)were 35.8±3.0 years and 20.1±1.9 kg/m2 in the control group and 35.8±2.7 years and 19.4±2.5 kg/m2 in the POI group,respectively.The mean gravidity and parity in control and POI groups were 0.6±0.7 and 0.4±0.5 and 0.6±0.9 and 0.3±0.5,respectively.The two groups did not differ significantly in terms of mean age,BMI,gravidity,or parity.The d-ROMs level was significantly higher in the POI group than in the control group(478.2±58.7 vs 341.1±35.1 U.CARR;P<0.001);however,the BAP level did not significantly differ between the two groups(2078.5±157.4 vs 2029.0±186.4μmol/L).The oxidase stress index(d-ROMs/BAP×100)was significantly higher in the POI group than in the control group(23.7±3.3 vs 16.5±2.1;P<0.001).CONCLUSION Oxidative stress was significantly greater in the POI group than in the control group,suggesting oxidative stress as a factor that can serve as a POI biomarker.
文摘Premature ovarian insufficiency,as a complex gynaecological disease,seriously threatens the physical and mental health of women of childbearing age.The main reasons for its pathogenesis are summarized.As a complex gynaecological disease,premature ovarian insufficiency seriously threatens the physical and mental health of women of childbearing age.The causes of the disease mainly include genetic defects,autoimmune disorders,radiotherapy and chemotherapy,infection,surgery,adverse environmental exposures and other factors.In more than half of cases,the cause remains unclear.In the clinic,hormone replacement therapy is used mainly to relieve the symptoms of oestrogen deficiency.This article reviews the research progress on the causes and treatment of premature ovarian insufficiency in recent years.
基金the Research Grant from the Natural Science Research Program of Shanxi Province:Based on Ultra-Performance Liquid Chromatography-Mass Spectrometry,the effect of"Zhibian(BL54)through Shuidao(ST28)"Needle Method on Ovarian Metabolism and Apoptosis Pathways in rats with Premature Ovarian Insufficiency was Discussed(No.2022030211216)。
文摘OBJECTIVE:To analyze the serum metabolic targets of the"Zhibian(BL54)through Shuidao(ST28)"acupuncture technique in cyclophosphamide(CTX)-induced premature ovarian insufficiency(POI)model rats and to elucidate the potential molecular mechanism of acupuncture in improving POI.METHODS:We used an intraperitoneal injection of CTX to establish the POI rat model(POI group)and compared serum hormone levels and ovarian histopathological changes to evaluate the effect of the Zhibian(BL54)through Shuidao(ST28)technique(ZS+POI group)on ovarian function.Then,nontargeted metabolomics was performed using rat serum by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS).RESULTS:After acupuncture intervention,the serum hormone levels and ovarian pathological morphology of POI rats were effectively improved.Moreover,UPLC-Q-TOF/MS results showed that the ZS+POI group showed a significant reversal of the levels of 6 differential metabolites.Among them,the levels of four serum metabolic markers,divanillyltetrahydrofuran ferulate,trans-ferulic acid,tryptamine,and neuraminic acid,increased significantly.Further analysis of biological effects showed that all metabolites were involved in the regulation of reproductive hormone levels and antioxidant and antiapoptotic effects.CONCLUSIONS:The"Zhibian(BL54)through Shuidao(ST28)"acupuncture method may improve the ovarian function of POI rats by regulating serum metabolite markers to exert antioxidant and antiapoptotic effects,which provides a theoretical basis for the clinical application of acupuncture in the treatment of POI.
基金This work was financially supported by Postgraduate Scientific Re-search Foundation of Zhejiang Chinese Medical University[Number:2020YKJ12].
文摘Background:The prevalence of premature ovarian insufficiency(POI)is gradually increasing,safer and more effective treatments are urgently needed.Objective:The aim of this study was to evaluate the effects of Ningxin-Yishen formula(NXYSF)on D-galactose-induced POI mice as well as to shed a light on its potential mechanisms.Methods:Six to eight weeks old female C57BL/6 mice were used in this study and randomly divided into six groups:control group;model group;estradiol valerate(EV)treatment group and NXYSF treatment group with graded doses(9.5,19,and 38 g·kg^(−1)/d).Both EV and NXYSF treatments were initiated at the 15th day of modeling and lasted for 28 days.Afterwards,the ovarian function was evaluated in each group by analyzing the proportion of primordial follicles as well as the serum sex hormone levels.Furthermore,network pharmacology approach was performed to elucidate the potential targets of NXYSF,which was verified through western blotting experiments finally.Results:NXYSF could significantly reverse the inefficiency of weight gain caused by POI,and promote the devel-opment of primordial follicles.In addition,it could restore the abnormal serum anti-Müllerian hormone(AMH),estradiol(E 2),luteinizing hormone(LH)and follicle-stimulating hormone(FSH).Moreover,some crucial key gene targets including TP53 were as propose to be relate with the effect of NXYSF through network pharmacology anal-ysis.Last but importantly,western blotting experiments confirmed that NXYSF could inhibit the expression of p53 protein in mouse ovaries.
文摘Background:Premature ovarian insufficiency(POI)is a common refractory disease in gynecology,and its etiology and pathogenesis are complex.Psychological stress exerts an impact on women’s physical and mental health,and in turn affects the ovarian reserve function,which is one of the important etiologies and pathogenesis of POI.The compound formula Ningxin Tongyu Zishen Tang(NTZT)is composed of Chinese herbal medicines which can nourish heart and tranquilize mind,tonify kidney and supplement essence.By comparing the menstrual symptoms,traditional Chinese medicine(TCM)symptoms and the levels of serum sex hormone before and after treatment,the NTZT is clarified for its curative effect and advantages in patients with POI.Objective:The study aimed to observe the effects of NTZT on menstrual symptoms,TCM symptoms and the levels of serum sex hormone in POI patients.Methods:60 POI patients were divided into two groups,namely observation group and control group,with 30 patients in each group.The patients in both groups were treated by hormone replacement therapy(HRT).The observation and control groups received treatment with NTZT and or Liuwei Dihuang Wan(LDW),respectively.All of the patients were treated for 3 months continuously.The menstrual symptoms,TCM symptoms and the levels of serum sex hormone of the two groups were investigated before and after treatment.Results:It was found that the menstrual symptoms,TCM symptoms and the levels of serum sex hormone improved dramatically after treatment in the observation group(P<0.01).By comparison,the menstrual symptoms and the levels of serum sex hormone improved significantly(P<0.01),but no obvious improvement in TCM symptoms(P>0.05)in the control group was observed.Compared with the control group,the observation group showed significant improvement in TCM symptoms and the levels of serum sex hormone(P<0.01),but no significant difference was observed in the menstrual symptoms(P>0.05).In addition,there was no any adverse events such as gastrointestinal dysfunction and drug allergyobserved in both groups,indicating the safety of the two TCM formulas.Conclusion:The study found that NTZT could restore menstruation and improve the levels of sex hormone in patients with POI.It was also found that NTZT could eliminate the feelings of vexation,insomnia and dream-fulness,as well as tidal fever and sweating,aching pain of loins,and vaginal dryness significantly.It can be proved that NTZT is effective in treating patients with POI owing to its effects of nourishing heart and tranquil-izing mind,tonifying kidney and supplementing essence together,leading to elimination of psychological stress,which further promotes the development of the ovaries.
基金Supported by China Academy of Chinese Medical Sciences:ZZ0908019
文摘Objective To systematically evaluate the effectiveness and safety of acupoint stimulation therapy for treatment of premature ovarian insufficiency（POI）. Methods Computer retrieval was carried out in such databases as Pub Med, Embase, Cochrane Library, web of science, Chinese biomedicine database（CBM）, China National Knowledge Infrastructure（CNKI）, Wan Fang and VIP in order to collect the randomized controlled trials（RCT） concerning acupoint stimulation therapy for treatment of POI. Software R 3.40 and stata 14.0 were used for Meta-analysis and network Meta-analysis, and Rev Man 5.3 was used for plotting the risk bias diagrams. Results Fortythree RCTs were included in total, involving 3046 POI patients and 18 acupoint stimulation therapies and comprehensive therapies. Metaanalysis showed：（1） The curative effects of acupoint stimulation therapy（RR=1.25, 95%CI [1.07,1.45]）, acupoint stimulation therapy＋Chinese herbal medicine（RR=1.25, 95%CI [1.18,1.32]） and acupoint stimulation therapy＋ hormone replacement therapy（HRT）（RR=1.20, 95%CI [1.12,1.29]） were all superior to that of HRT, indicating that the differences were statistically significant（Z=2.90, P=0.04; Z=7.56, P〈0.000 01; Z=4.06, P〈0.000 01）.（2） Compared with HRT, the occurrence rate of adverse effect of acupoint stimulation therapy was lower, and the safety was superior to that of HRT（RR=0.18, 95%CI [0.08,0.41]）, indicating that the differences were statistically significant（Z=4.08, P〈0.000 1）. Forty-two direct comparisons and 110 indirect comparisons were generated according to network Meta-analysis, among which, 38 comparisons were statistically significant. Network Metaanalysis results with HRT as control showed： the therapeutic measures ranking top 3 according to the curative effect sequence were catgut embedment in acupoint, moxibustion and warming-needle moxibustion, successively, and all the 3 measures were monotherapies without reflecting the advantages of comprehensive therapy. HRT ranked 17 th among the 18 included therapeutic measures. Conclusion On the basis of current evidences, acupoint stimulation therapy has a better clinical efficacy and safety for treatment of POI when compared with HRT. The acupoint stimulation therapies ranking the top 3 have more significant curative effects, but the long-term efficacy and the effect on the ovarian function still need to be further explored. In addition, the conclusion of this study still needs to be verified through a large number of RCTs with reasonable designs and appropriate methods.
基金Supported by National Key R&D Program of China2019YFC1712200International standards research on clinical research and service of AcupunctureMoxibustion2019YFC1712205。
文摘Objective:To assess the reliability of the methodological quality and outcome measures of systematic reviews(SR)/meta-analysis of premature ovarian insufficiency(POI) treated with acupuncture.Methods:SR/meta-analysis of POI treated with acupuncture were searched on POI from the databases including PubMed,Web of Science,EMBase,the Cochran Library,Chinese biomedical literature database(SinoMed),China journal full-text database(CNKI),Wanfang data knowledge service platform(Wanfang)and VIP information Chinese periodical service platform(VIP),from inception to 1 st May 2021.Using A Measurement Tool to Assess Systematic Reviews 2(AMSTAR 2) scale and Grades of Recommendations Assessment,Development and Evaluation(GRADE) system,the methodological quality and outcome measures of the included studies were appraised.Results:Ten articles of SR/meta-analysis were included,published from 2015 to 2020.Using AMSTAR 2,5 articles of SR/meta-analysis were rated as critical low quality in methods,3 articles as low quality,and2 articles as moderate quality.The results of GRADE showed that among the 50 outcomes the quality of evidence of 22 outcomes was very low,that of 25 outcomes was low and that of 3 outcomes was moderate.Conclusion:The methodological quality and the reliability of outcome measures were not high in existing SR/meta-analysis on POI treated with acupuncture,which may affect the translation of the SR/metaanalysis findings into clinical practice.It is necessary to further strengthen the methodological quality and reporting standard of SR/meta-analysis,as well as the robustness of design and implementation of randomized controlled trials(RCTs),in order to generate high quality evidences for clinical decision-making and practice.
文摘Objective:To analyze the effect of acupuncture versus hormone replacement therapy(HRT)for premature ovarian insufficiency(POI).Methods:China National Knowledge Infrastructure(CNKI),Wanfang Academic Journal Full-text Database(Wanfang),Chongqing VIP Database(CQVIP),China Biology Medicine Disc(CBM),Web of Science,Cochrane Library,PubMed,and Excerpta Medica Database(EMBASE)were searched up to January 31st,2019 to identify randomized controlled trials(RCTs)evaluating the effect of acupuncture for POI.The primary outcome was the level of basal serum follicle-stimulating hormone(FSH).Secondary outcomes included serum levels of luteinizing hormone(LH),estradiol(E2)and anti-Müllerian hormone(AMH).Two authors extracted data independently and assessed the risk of bias and the methodological quality using the Cochrane's tool.Meta-analysis was conducted by RevMan version 5.3.Results:Eight eligible RCTs with a total of 496 POI patients were included in the meta-analysis.The pooled results showed that there was a significant reduction in the basal serum FSH level(MD=-5.82,95%CI:-9.76 to-1.87,I2=82%,P=0.004)and a remarkable elevation in the basal E2 level(SMD=0.93,95%CI:0.34 to 1.52,I2=88%,P=0.002)in the acupuncture group when compared with the control.Subgroup analysis showed that compared with HRT,a significant decrease in the FSH level was observed in both acupuncture alone(MD=-4.53,95%CI:-8.96 to-0.10,I2=73%,P=0.04)and acupuncture plus HRT(MD=-9.60,95%CI:-17.60 to-1.61,I2=50%,P=0.02),while a remarkable elevation of E2 was only found in acupuncture plus HRT(SMD=1.43,95%CI:1.03 to 1.82,I2=0%,P<0.00001).There was no significant difference in the LH level between acupuncture and HRT(MD=-3.16,95%CI:-9.41 to 3.10,I2=0%,P=0.32),only one trial reported AMH,and no significant difference was found between acupuncture and HRT.Conclusion:The present study indicated that acupuncture had an advantage over HRT in reducing serum FSH level and increasing serum E2 level in women with POI.However,evidence supporting the finding is limited due to the small sample size,potential methodological flaws and significant heterogeneity.Hence,this conclusion still needs to be verified by high-quality RCTs.
基金Supported by Ministry of Science and Technology of the People's Republic of China through the Twelfth Five-Year National Science and Technology Pillar Program(2012BAI24B02)~~
文摘Premature ovarian insufficiency（POI） affects seriously physical and mental health of the patients. Studies show that acupuncture may be promising in treating POI. yet evidence is insufficient. International patient registry, one form of observational study, is designed for evaluating effectiveness and safety of acupuncture in real-world clinical settings. We will face a series of opportunities and challenges. The opportunities are as follows：（1） Interdisciplinary cooperation can improve the effect of acupuncture for POI.（2） The protocol for acupuncture to treat POI has room for improvement.（3） The patient registry study can make up the shortcomings of randomized controlled trials.（4） The patient registry study can collect real-world data and explore responses of different populations to acupuncture and can be the foundation for the successive studies. International patient registry may face technological, ethical and financial challenges, while the established International Patient Registry Platform of Acupuncture-Moxibustion（www.amreg.org：8082/v3） is actively responding to these challenges. Till now there have been more than 300 patients of POI enrolled on this platform.
基金This work was supported by the Science Fund of the Republic of Serbia(IDEAS),Project Number:7750154(NPATPETTMPCB).Project Title:New Prognostic and Theranostic Potential of Enzymes Involved in CoTranscriptional Cleavage and Co-Translational Modification in Prostate,Colorectal,and Breast Cancer Tissue.
文摘Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality.The effect of chemotherapy can range from minimal effects to complete ovarian atrophy.Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility.Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist(GnRHa)during chemotherapy decreases the gonadotoxic effect of chemotherapy,thereby diminishing the chance of developing premature ovarian insufficiency(POI).At present,the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function.Notably,most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer,with a considerably small number of studies on patients with hematological malignancies.Furthermore,most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk,regardless of the hormone receptor status.In addition,studies on hematological malignancies have yielded negative results;nevertheless,thefindings must be interpreted with caution owing to numerous limitations.Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm,oocyte,and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible.In this manuscript,we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data,as well as future perspectives in thisfield that upcoming research should focus on.
文摘Hormone therapy,assisted reproductive technology,and regenerative medicine have been used to treat infertility due to premature ovarian insufficiency(POI),with limited success.It is timely to survey the field by outlining the controversies and promising prospects of evolving stem cell(SC)therapy for patients with POI.We first discuss several strategies of tissue-derived SC therapy and induced/engineered SC therapy and then enumerate mechanisms,including cellular regenerability induced in reproductive tissues and paracrine effects induced by various chemokines.Next,we evaluate the potential benefits of SC-based tissue engineering in reversing ovarian aging.Finally,we discuss the clinical feasibility of SC therapy and generalized regenerative medicine for the treatment of POI.In summary,SCs and SC-derived exosomes,induced pluripotent SCs,engineered SCs,and tissue engineering could start a new chapter for fertility rehabilitation in patients with POI.Uncovering the underlying molecular mechanisms and biological efficacy could be facilitated not only by animal experiments but also by security screening and clinical trials to validate SC-based therapy for POI.
基金funded by the National Natural Science Foundation of China(No.81471423)to Bin Li。
文摘Objective:Mutations in NUP107 have been discovered in patients with premature ovarian insufficiency and may have tissue-specific effects in ovarian development.However,the role of NUP107 in human granulosa cell(GC)function and female fertility still remains unknown.In this study,we used RNA interference to investigate how NUP107 dysfunction influences GCs and ovarian development.Methods:Immunohistochemical staining was used to detect the expression of NUP107 in ovaries.Cell counting kit-8 assay,real-time cell analysis,and flow cytometry were used to explore cell proliferation and apoptosis,and an enzyme-linked immunosorbent assay was used to assess the estrogen concentrations.Quantitative real-time reverse transcription-quantitative polymerase chain reaction and Western blot analyses were used to determine the expression of NUP107 and functional receptors.Results:Knockdown of NUP107 expression had little effect on the growth and number of GCs.Further study confirmed that knockdown of NUP107 may interfere with estrogen synthesis in GCs and their sensitivity to the regulation of follicle-stimulating hormone(FSH)by decreasing the expression of estrogen synthesis-related genes AR,CYP17A1,CYP19A1,STAR,and NR5A1.Moreover,knockdown of NUP107 decreased the expression of AMHR2,FSHR,LHR,and ESR1 in GCs,but had no effect on the expression of ESR2.Conclusions:These data revealed that NUP107 may impede follicle growth and maturation by regulating hormone synthesis,sensitivity to follicle-stimulating hormone,and expression of functional receptors in GCs,and may,therefore,interfere with female fertility.
基金supported by the CUHK VC Discretionary Fund provided to the Hong Kong Branch of Chinese Academy of Science Center for Excellence in Animal Evolution and Genetics(Acc 8601011)the National Key R&D Program(2021YFC2700500)A-Smart Group to Shandong University and SDIVF R&D Centre Hong Kong,and Research Grants Council General Research Fund(Hong Kong Special Administrative Region Government)(14103418)。
文摘Chemotherapy can significantly reduce follicle counts in ovarian tissues and damage ovarian stroma,causing endocrine disorder,reproductive dysfunction,and primary ovarian insufficiency(POI).Recent studies have suggested that extracellular vesicles(EVs)secreted from mesenchymal stem cells(MSCs)exert therapeutic effects in various degenerative diseases.In this study,transplantation of EVs from human induced pluripotent stem cell-derived MSCs(iPSC-MSC-EVs)resulted in significant restoration of ovarian follicle numbers,improved granulosa cell proliferation,and inhibition of apoptosis in chemotherapy-damaged granulosa cells,cultured ovaries,and in vivo ovaries in mice.Mechanistically,treatment with i PSC-MSC-EVs resulted in up-regulation of the integrinlinked kinase(ILK)-PI3K/AKT pathway,which is suppressed during chemotherapy,most likely through the transfer of regulatory microRNAs(miRNAs)targeting ILK pathway genes.This work provides a framework for the development of advanced therapeutics to ameliorate ovarian damage and POI in female chemotherapy patients.
文摘OBJECTIVE:To investigate the efficacy of needling acupoins of Guanyuan(CV4),Sanyinjiao(SP6),Zusanli(ST36),Pishu(BL20),Shenshu(BL23),Zigong(EX-CA1)on the expression of p38 mitogen-activated protein kinase(p38MAPK)in ovarian tissue in rats with premature ovarian failure induced by cyclophosphamide,and to study the underlying mechanism.METHODS:Forty specific pathogen free female Sprague-Dawley rats were randomly divided into the blank group,the model group,the acupuncture group,the Western Medicine group and the Western Medicine combined with acupuncture group.Except the blank group,the rest of the rats were given with cyclophosphamide for 14 d to establish premature ovarian failure model.No intervention was conducted in the blank group and model group;the acupuncture group was given with acupuncture daily;the Western Medicine group was given with estradiol valerate(0.09 mg/kg)by intragastrical gavage daily;the combination group was given with acupuncture combined with estradiol valerate(0.09 mg/kg)daily.Each group was intervened in continuously for 14 d.After the last treatment,the levels of estradiol(E2),follicle stimulating hormone(FSH)and luteinizing hormone(LH)were detected by enzyme-linked immunosorbent assay,then the ovarian tissue was dissected.Western blot was used to detect the expression of p38 MAPK protein.RESULTS:Compared with the blank group,E2 in the serum of rats in the model group was significantly decreased(P<0.05),FSH and LH were significantly increased(P<0.05),and the expression of p38 MAPK protein in the ovarian tissue of the rats was significantly increased(P<0.05).Compared with the model group,E2 in the serum of the acupuncture group,Western Medicine group and the combination group were significantly increased(P<0.05),FSH and LH levels were significantly decreased(P<0.05),and the expression of p38MAPK protein in the ovarian tissue of the rats was significantly decreased(P<0.05).However,there was no statistically significant difference between the Western Medicine group and the acupuncture group(P>0.05).CONCLUSIONS:Acupuncture has the same effect as estrogen in interfering POF caused by cyclophosphamide,and its mechanism may be related to inhibiting the expression of p38MAPK protein in ovarian tissue and affecting the activation of p38MAPK signaling pathway.
文摘In India</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> the problem of infertility is growing and in the last 5 years</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> it has gone up to 20%</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">-</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">30%. This ongoing prospective clinical study brings forth a novel, innovative, effective, simple, affordable, easily performed outpatient procedure (OP) and a promising therapeutic method in rejuvenating the Ageing Ovaries and Thin Endometrium, with autologous Platelet Rich Plasma (PRP). This clinical study proves to give a better result in rejuvenating Ovary and treating the Thin Endometrium. This pilot study include</span><span style="font-family:Verdana;">d</span><span style="font-family:Verdana;"> five women (28</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">-</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">44 years) with Poor Ovarian Response (POR), Premature Ovarian Insufficiency (POI) and Perimenopause and Thirty-nine women (22</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">-</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">43</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">years.) with recurrent implantation failure due to Thin Endometrium were subjected to autologous PRP instillation under Ultrasound Guidance, and Hysteroscopic guided PRP. After PRP</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> a significant output was obtained, with improved Anti Mullerian Hormone (AMH) and Antral Follicle Count (AFC) and out of five women three women conceived by Intra Cytoplasmic Sperm Injection (ICSI). PRP injected in women with Poor Ovarian Response found successful ovarian rejuvenation within 1</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">-</span><span style="font-size:10pt;font-family:""> </span><span style="font-family:Verdana;">3 months and had a 60% of pregnancy rate, PRP into the endometrium had 53.8% successful pregnancies. We have not encountered any complications.
基金supported by Project No.15.BRK.21.008 Multicenter Research Bioresource Collection“Human Reproductive Health”(Agreement No.075-15-2021-1058 dated September 28,2021)funded by the Ministry of Science and Higher Education of the Russian Federation.
文摘Successful reproduction in mammals requires gamete development,fertilization,and early embryonic development.Defects in any of these processes can lead to infertility,recurrent miscarriages,and congenital defects.The clinical recognition of the genetic causes of female reproductive insufficiency using increasingly advanced genetic technologies poses a serious challenge for reproductive medicine in the 21st century.Herein,the current literature on genetic factors involved in reproductive losses was summarized.A literature search was conducted using Web of Science,MEDLINE,and PubMed databases for articles written in English on the genetic causes of women’s reproductive health disorders.Future implementation of whole-exome and wholegenome sequencing is expected to identify numerous genetic factors responsible for oocyte quality.Which will aid in increasing the likelihood of successful female reproductive function,improve the outcomes of assisted reproductive technologies,optimize treatment,and facilitate genetic diagnosis of patients.
基金supported by grants from the National Key R&D Program of China(2018YFC1003700,2018YFC1003800,and 2017YFC1001100)the National Natural Science Foundation of China(31872792,31371448,and 31571540)+2 种基金Beijing Natural Science Foundation(5182015 and 7182090)Project of State Key Laboratory of Agrobiotechnology(2015SKLAB4-1 and 2016SKLAB-1)Institution of Higher Education Projects of Building First-class Discipline Construction in Ningxia Region(NXYLXK2017B05).
文摘Establishment of the primordial follicle(PF)pool is pivotal for the female reproductive lifespan;however,the mechanism of primordial folliculogenesis is poorly understood.Here,the transcription factor SP1 was shown to be essential for PF formation in mice.Our results showed that SP1 is present in both oocytes and somatic cells during PF formation in the ovary.Knockdown of Sp1 expression,especially in pregranulosa cells,significantly suppressed nest breakdown,oocyte apoptosis,and PF formation,suggesting that SP1 expressed by somatic cells functions in the process of primordial folliculogenesis.We further demonstrated that SP1 governs the recruitment and maintenance of Forkhead box L2-positive(FOXL2^+)pregranulosa cells using an Lgr5-EGFP-IRES-CreER^T2(Lgr5-KI)reporter mouse model and a FOXL2^+ cell-specific knockdown model.At the molecular level,SP1 functioned mainly through manipulation of NOTCH2 expression by binding directly to the promoter of the Notch2 gene.Finally,consistent with the critical role of granulosa cells in follicle survival in vitro,massive loss of oocytes in SP1 knockdown ovaries was evidenced before puberty after the ovaries were tranSP1anted under the renal capsules.Conclusively,our results reveal that SP1 controls the establishment of the ovarian reserve by regulating pregranulosa cell development in the mammalian ovary.
