Endometrial receptivity is an important factor that influences embryo implantation.Thus,it is important to identify an applicable approach to improve endometrial receptivity in women undergoing assisted reproductive t...Endometrial receptivity is an important factor that influences embryo implantation.Thus,it is important to identify an applicable approach to improve endometrial receptivity in women undergoing assisted reproductive technology.Recently,growing evidence has indicated that intrauterine platelet-rich plasma(PRP)infusion is an effective method to obtain a satisfactory reproductive outcome by increasing endometrial thickness and improving endometrial receptivity.Therefore,the present review aims to outline the possible mechanisms of PRP on endometrial receptivity and summarize the present literature on the effects of PRP therapy in improving endometrial receptivity.展开更多
This study examined the impact of luteinized unruptured follicle （LUF） on endometrial receptivity. The menstrual cycle of 17 LUF patients （LUF group） and 13 ovulatory women （control group） was monitored by measu...This study examined the impact of luteinized unruptured follicle （LUF） on endometrial receptivity. The menstrual cycle of 17 LUF patients （LUF group） and 13 ovulatory women （control group） was monitored by measuring LH level in urine and by ultrasonic examination. An endometrial biopsy at the sixth to tenth day after LH surge was taken in all the patients. The expressions of endometrial ER, PR and integrin ανβ3 were immunohistochemically determined. At the same time, the serum levels of E2 and P were detected by chemiluminescence. The results exhibited that （1） The mean serum P level in LUF group （7.32±2.56 ng/mL） was significantly lower than that in control group （11.17±3.17 ng/mL） （P0.01）. But there was no significant difference in the mean serum E2 levels between LUF group （179.35±81.60 pg/mL） and the control group （198.58±75.23 pg/mL） （P0.05）; （2） The mean expression intensities of ER, PR in endometrium of LUF group （183.86±2.43, 167.94±3.04） were significantly higher than those in control group （109.35±6.31, 105.98±4.07） （P0.01）; （3） The mean expression intensities of integrin ανβ3 in endomtrium of LUF patients （114.90±11.38） were significantly lower than those in control group （191.34±1.82） （P0.01）; （4） The change profile of integrin ανβ3 expression in the endometrium of LUF patients was in positive relation with serum P level （r=0.77, P0.01）, but bore no significant relationship with serum E2 level （r=0.01, P0.05）. It was concluded that the depression of serum P levels in LUF patients was closely related to the failure of the down-regulation of ER and PR, and the low expressions of integrin ανβ3 also suggested that the delayed implantation and the impaired endometrial receptivity had impact on embryonic implantation.展开更多
Objective:Bushen Chengyun granule(BCG)is an empirical treatment for female infertility(FI)caused by low endometrial receptivity(LER)involving a poorly understood mechanism.In this study,network pharmacology was used t...Objective:Bushen Chengyun granule(BCG)is an empirical treatment for female infertility(FI)caused by low endometrial receptivity(LER)involving a poorly understood mechanism.In this study,network pharmacology was used to explore the potential therapeutic mechanism of BCG on FI caused by LER.Methods:The corresponding herb targets were obtained by conducting a search in the Traditional Chinese Medicine Systems Pharmacology Database and PubMed-reported literature.Disease targets were obtained from the following databases:Comparative Toxicogenomics Database,Human Phenotype Ontology,and Therapeutic Target Database.Treatments for LER using BCG have used target matching(BCG e LER target).Then,the predicted targets were uploaded to the Search Tool for the Retrieval of Interacting Genes/Proteins database for gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses.Furthermore,triptorelin acetate for injection t menotrophin t chorionic gonadotropin for injection were used to establish a mouse model of blastocyst implantation disorder and to evaluate the in vivo effect of BCG on blastocyst implantation.Results:Overall,156 bioactive chemical components and 1092 targets of BCG were identified.The results indicated that 482 biological processes(FDR<0.01)and 15 pathways(FDR<0.01)related to BCG participated in the complex treatment effects and were associated with the endocrine system,inflammatory responses,metabolism,apoptosis,ovulatory performance,and angiogenesis.Moreover,16 hub nodes of BCG including estrogen receptor(ESR1),estrogen receptor beta(ESR2),progesterone receptor,et al,were recognized as potential treatment targets and might help clarify the underlying therapeutic mechanisms of BCG for female infertility.BCG significantly increased the protein expressions of estrogen receptors and progesterone receptors.Conclusions:These findings reveal the potential therapeutic mechanism of BCG for female infertility involves low endometrial receptivity,which should be evaluated further.展开更多
Objective To study the effect of single and low dose of RU486 on endometrial receptivity of healthy women. Methods A total of 5 healthy women were followed for one control and one treatment cycle. In the treatment c...Objective To study the effect of single and low dose of RU486 on endometrial receptivity of healthy women. Methods A total of 5 healthy women were followed for one control and one treatment cycle. In the treatment cycle, a dose of 10 mg RU486 was administered on day luteinizing hormone (LH)-2. In both the control and treatment cycle, an endometrial biopsy was obtained on LH+7. These biopsies were assessed by immunohistochemical analysis to find the difference in expression of integrins and progesterone receptor (PR) between the control and treatment cycle. Results The treatment with RU486 increased the expression of α 1 and α 4 subunits of integrin in glandular epithelial cells, but did not influence β 3 subunit. Moreover, the normal down regulation of PR in epitherial cell nuclei was inhibited by 10 mg RU486. Conclusion Single dose of 10 mg RU486 impairs the establishment of endometrial receptivity on time.展开更多
Objective To establish the mice model of implantation dysfunction and to study the endometrial receptivity during implantation in implantation dysfunction mouse. Methods Sexually mature female virgin, Kunming mice wer...Objective To establish the mice model of implantation dysfunction and to study the endometrial receptivity during implantation in implantation dysfunction mouse. Methods Sexually mature female virgin, Kunming mice were randomly assigned to the control group and the model group postcoitally. The model mice at 9 ： 00 AM on d 4 of pregnancy（d 4） were injected subcutaneously with mifepristone. All animals were sacrificed at 9 ：00 PM on d 4 and their uterine horns were examined for the presence of implanted embryos. Histopathology of uterine endometrium was observed by light-microscope. The endometrial expressions of estrogen receptor （ER） and progesterone receptor （PR） assessed by immunnohistochemical SP method. The endometrial expressions of ER mRNA and PR mRNA were assessed by semi-quantitative reverse transcriptase polymerase chain reaction （RT-PCR）. Results Compared with control group, implantation rates and average embryo num- ber significently decreased in model group, the development of endometrium was inhibited. In model group, absorbency and area rate of ER and PR in the gland and stroma were lower than those in control group （P〈0.05）. Expressions of ER mRNA and PR mRNA in model uterus were significantly lower than those in the control. Conclusion The endometrial receptivity and implantation decreased in mifepristoneinduced implantation dysfunction mouse.展开更多
Objective: To systematically evaluate the efficacy and safety of Bushen Recipe combined with clomiphene compared with clomiphene in improving endometrial receptivity of polycystic ovary syndrome. Methods: The time lim...Objective: To systematically evaluate the efficacy and safety of Bushen Recipe combined with clomiphene compared with clomiphene in improving endometrial receptivity of polycystic ovary syndrome. Methods: The time limit is from the establishment of the database to January 2, 2020. A randomized controlled trial was conducted to compare the effects of Bushen Recipe combined with clomiphene and clomiphene on the endometrial receptivity of polycystic ovary syndrome (PCOS). Meta analysis was performed with RevMan5.3 software. Results: A total of 13 RCTS were included, with a total of 797 PCOS patients. The results of this meta-analysis show: there were statistically significant differences in the improvement of endometrial thickness [WMD=1.62,95%CI(1.22, 2.01), P <0.00001], endometrial type[RR=1.51,95%CI(1.28, 1.78), P <0.00001], uterine artery pulse index(PI) [WMD=-0.18,95%CI(-0.27, -0.09) , P <0.0001], uterine artery resistance index(RI)[WMD=-0.08,95%CI(-0.11, -0.05) , P <0.00001], pregnancy rate [RR=2.18,95%CI(1.55, 3.05), P <0.00001], TCM syndrome score[WMD=-6.97,95%CI(-8.97, -4.97) , P <0.00001], effective rate [RR=1.25, 95%CI (1.13, 1.37), P < 0.00001]. Conclusion: Compared with clomiphene alone, Bushen Recipe combined with clomiphene can effectively increase the thickness of endometrium and improve the type of endometrium, promote the blood perfusion of endometrium, improve the pregnancy rate, improve the clinical symptoms, reduce the TCM syndrome score, improve the total efficiency of treatment, with high clinical application value.展开更多
Successful implantation requires concerted interactions during the apposition,adhesion,and invasion of the embryo into a receptive endometrium.However,the embryo implantation rate for assisted reproduction remains low...Successful implantation requires concerted interactions during the apposition,adhesion,and invasion of the embryo into a receptive endometrium.However,the embryo implantation rate for assisted reproduction remains low despite the transfer of good quality embryos.Changes in endometrial transcriptomics,proteomics,lipidomics,and even microbiota all play important roles in embryo implantation.Specifically,the expression of steroid hormone-regulated adhesive and anti-adhesive molecules during the embryo implantation window is becoming an area of increasingly intense research.This review(a)summarizes the different molecules expressed in the receptive endometrium and(b)proposes the use of surface protein markers to predict pregnancy outcomes from assisted reproduction.展开更多
Background: Rhizoma drynariae is a traditional Chinese medicine used in orthopedics and traumatology, but its effect on endometrial receptivity remains unknown. Aims and Objectives: To observe effect of Rhizoma drynar...Background: Rhizoma drynariae is a traditional Chinese medicine used in orthopedics and traumatology, but its effect on endometrial receptivity remains unknown. Aims and Objectives: To observe effect of Rhizoma drynariae and its main components on endometrial receptivity in a mus model of dysfunctional embryo implantation. Materials and Methods: Mus models were established by the Gn RHa+HMG+HCG method. Normal mus receiving saline were used as controls and the remaining six groups were: model receiving saline, progynova, aspirin, Rhizoma drynariae, osteopractic total flavone, and naringin. Pinopodes in uterine endometrium were examined by scanning electron microscopy. Stem cell factor(SCF) m RNA expressions was determined by real-time RT-PCR, and estrogen receptor α(ERα), progesterone receptor(PR) by immunohistochemistry. Results: In the model group, surface morphology of endometrium was heterogeneous, without obvious pinopodes. In the Rhizoma drynaria and progynova groups, pinopodes were abundant. Compared with the blank group, model group had lower levels of SCF(-47%), ERα(-63%) and PR(-50%)(all P<0.05). In comparison, Rhizoma drynariae group had higher levels of SCF(+73%), ERα(+118%) and PR(+101%)(all P<0.01). The individual main components of Rhizoma drynariae had variable efficacy. Conclusion: Rhizoma drynariae could improve endometrial receptivity of mouse models of dysfunctional embryo implantation as shown by increased numbers of pinopodes and higher levers of SCF, ERα, PR compared with the model group.展开更多
Objective To observe acupuncture effects on endometrial receptivity of the rats with polycystic ovary syndrome （PCOS） treated by ovarian stimulation with Clomiphene to explore its mechanisms. Methods eGOS rat model ...Objective To observe acupuncture effects on endometrial receptivity of the rats with polycystic ovary syndrome （PCOS） treated by ovarian stimulation with Clomiphene to explore its mechanisms. Methods eGOS rat model was experimentally induced by subcutaneous injection of oil solution of dehydroepiandrosterone （DHEA） in immature （24-day-old） female rats for continuous 20 days. The same dose of oil was given for an equivalent length of time to animals in a control group （Group Con）. The rats with PCOS were randomly divided into a model group （group M）, a Clomiphene treatment group （group C）, a Clomiphene plus acupuncture group （group C＋ A）. The treatments were given for 5 days since 80 days after birth. Half of the rats were killed by decapitation after treatment finished, and the serum, uteri and endometria were obtained. The other half mated with male rats, and they were killed at the 8th day of pregnancy. We observed the implantation number and condition of pregnant uteri. Results Compared with group C, the animals in group C＋A had higher implantation rate and more average implanted embryos （P〈0. 01 ）, higher serum estradiol （E2） level （P〈0.01 ）, better development of endometrium, and increased mRNA and protein expressions of molecular markers of endometrial receptivity （P〈0.01）, which were closer to those in the control group. Conclusion Acupuncture could improve poor endometrial receptivity of PCOS rats with ovarian stimulation by citrated Clomiphene and promote implantation. The effects may be related with its up-regulation of serum E2 level, mRNA and protein expressions of molecular markers of endometrial receptivity.展开更多
Objective:To observe the effect of the combined therapy of electroacupuncture(EA) and ginger-isolated moxibustion on endometrial receptivity in the patients with polycystic ovarian syndrome(PCOS).Methods:A total of 70...Objective:To observe the effect of the combined therapy of electroacupuncture(EA) and ginger-isolated moxibustion on endometrial receptivity in the patients with polycystic ovarian syndrome(PCOS).Methods:A total of 70 subjects of PCOS were randomized into two groups,35 cases in each one.In the western medication group,letrozole and human chorionic gonadotropin(HCG) were administered.In the combined therapy group,on the base of the treatment as the western medication group,the artificial cycle therapy with EA and ginger-isolated moxibustion was provided.The treatment duration was 3 menstrual cycles in two groups.After treated for 3 menstrual cycles,the symptom score of traditional Chinese medicine(TCM),endometrial thickness,the number of ovulation cycle,endometrial morphology,bilateral uterine artery pulsatility index(PI),resistance index(RI),the sum of peak systolic velocity/end diastolic velocity(S/D) and pregnancy were compared in the patients between two groups.Results:(1) After treatment,the endometrial thickness was better(0.21 ± 0.13 vs 0.14 ± 0.08,P <0.01),TCM symptom score reducing range was larger(5.00 ± 2.24 vs 0.52 ± 1.66,P <0.01),the reducing degrees of bilateral uterine artery PI,RI and S/D sum were better(0.62 ± 0.26 vs 0.04 ± 0.15,0.08± 0.05 vs0.01±0.05,0.61±0.33 vs 0.07±0.17,0.11±0.05 vs 0.01 ± 0.05,4.80±1.14 vs 0.15 ± 0.89,all P <0.01) in the combined therapy group respectively as compared with the western medication group.After treatment,the number of ovulation cycle and the proportion of A+B type of endometrial morphological were higher in the combined therapy group(2.09 ± 0.78 vs 1.27 ± 0.84,87.5% vs 60.61%,P <0.01,P <0.05) as compared with the western medication group respectively.(2) The clinical pregnancy rate was56.25% in the combined therapy group,better than 30.30% in the western medication group(P <0.05).The early abortion rate was 10.53% in the combined therapy group,lower than 50.00% in the western medication group(P <0.05).Conclusion:The combined treatment of electroacupuncture and ginger-isolated moxibustion with western medication effectively improves endometrial receptivity,increases clinical pregnancy rate and reduces early abortion rate in the patients with PCOS.展开更多
Diabetes is a complex metabolic disorder which can adversely affect reproductive function. SGK1 is found to be up-regulated in multiple tissues of diabetic patients. However, the effects of diabetes on endometrial SGK...Diabetes is a complex metabolic disorder which can adversely affect reproductive function. SGK1 is found to be up-regulated in multiple tissues of diabetic patients. However, the effects of diabetes on endometrial SGK1 expression and endometrial receptivity remain unknown. In this study, we established a streptozotocin-induced diabetic mouse model and observed reduced implantation sites, retarded development of pinopodes, increased SGK1, and aberrant expression of LIF and MUC1 in the endometrial epithelium. We injected the uterine lumen of normal mice with high-glucose solution and cultured endometrial cells in high-glucose medium to mimic intrauterine hyperglycemia. Both studies provided compelling evidence that hyperglycemia could lead to diminished embryo implantation and dysregulated SGK1, LIF and MUC1. Additionally, through over-expression of SGK1 in vivo and in vitro, we found that enhanced SGK1 also decreased LIF expression, increased MUC1 expression, and attenuated embryo implantation rate. We further identified that hyperglycemia-activated SMAD2/3 might be responsible for the enhancement of SGK1 and verified directly the interaction between SMAD3 and corresponding SMAD binding elements within SGK1 promoter. Taken together, our study confirmed the association between diabetes-related hyperglycemia and endometrial receptivity defects. Hyperglycemia-induced SGK1 has a tremendous role in this pathological process, rendering it as an attractive therapeutic target for diabetes-related reproductive disorders.展开更多
Objective To evaluate endometrial and subendometrial blood flows measured by vaginal color Doppler ultrasound as a predicator of endometrial receptivity in women undergoing IVF treatment. Methods A total of 119 infert...Objective To evaluate endometrial and subendometrial blood flows measured by vaginal color Doppler ultrasound as a predicator of endometrial receptivity in women undergoing IVF treatment. Methods A total of 119 infertile patients undergoing the first IVF/ICSI-ET cycle were recruited. Three groups were divided according to a color Doppler ultrasound examination performed on the day of hCG injection. Group A, endometrial and subendometrial blood flows were 2 branches and below; group B, endometrial and subendometrial blood flows were between 3 and 4 branches; group C, endometrial and subendometrial blood flows were 5 branches and above. Patients were transferred 1-3 embryos each. Demographic data, ovarian responses, endometrial thickness, PI, RI, development of embryo and IVF result among groups were compared. Results Demographic data, ovarian responses, endometrial thickness, PI, RI and development of embryo among groups have no significant difference. The pregnancy rate of group A was significantly lower than that of group B （P〈0.05） and group C （P〈0.01）. The implantation rate of group A was significantly lower than than of group C （P〈0.01）. There was no significant difference of the rate of pregnancy and implantation between group B and group C （P〉0.05）. Conclusion Endometrial and subendometrial blood flows measured by vaginal color Doppler ultrasound is a good predicator of pregnancy during IVF treatment. A good endometrial and subendometrial blood flows is benefit for the result of IVF.展开更多
This review summarizes the drugs and chemicals that may modulate embryo implantation.Non-hormonal molecules,including aspirin,improved endometrial blood flow,while low molecular weight heparin,vitamin E,sildenafil,and...This review summarizes the drugs and chemicals that may modulate embryo implantation.Non-hormonal molecules,including aspirin,improved endometrial blood flow,while low molecular weight heparin,vitamin E,sildenafil,and atosiban modulated the expression of endometrial genes.Hormonal factors,including human chorionic gonadotropin and growth hormones,can regulate the expression of endometrial receptivity markers.Other immunomodulatory molecules,including granulocyte colony-stimulating factor,peripheral blood mononuclear cells,autologous platelet-rich plasma,and intralipid and intravenous immunoglobulins,may improve implantation rate by modulating endometrial immune functions.Medicinal extracts of the Chinese herbs Paeonia lactiflora and Perilla frutescens increased the expression of leukemia inhibitory factors in endometrial epithelial cells.Recently,the use of the commercially available Library of Pharmacologically Active Compounds with a high-throughput screening method has provided an approach to screen for compounds that may potentially enhance or suppress embryo implantation.Whether these biomedical findings translate into clinical effects that enhance or suppress embryo implantation requires further investigation.展开更多
Objective: To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional(3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer(IVF-ET). Method...Objective: To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional(3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer(IVF-ET). Methods: Seventy patients undergoing IVF-ET were equally randomized into traditional or sham acupuncture treatment group for totally 4 days(from the day of oocyte aspiration to the day of embryo transfer) of treatment by random envelope method at the Reproductive Medicine Center and Outpatient Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology from January 2013 to December 2015. Patients in the traditional acupuncture group accepted traditional acupuncture methods with manual acupuncture, and Zhongji(CV3), Qihai(CV 6), Sanyinjiao(SP6), Taichong(LR 3), Tianshu(ST 25), Guilai(ST 29) and Zusanli(ST 36) were chosen. Patients at the sham acupuncture group accepted shallow acupuncture methods at 4 non-meridian points at each shoulder and upper arm. Outcome measures included endometrial ultrasonic indices such as vascularization index(VI), flow index(FI) and vascularization flow index(VFI), endometrial thickness and volume, subendometrial VI(sVI), subendometrial FI(sFI), subendometrial VFI(sVFI), implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births. Results: Finally, 34 patients in the traditional acupuncture group and 35 in the sham acupuncture group completed this trial. VI, FI and VFI of the traditional acupuncture group were significantly higher than those in the sham acupuncture group(P<0.05). No significant differences were found in endometrial thickness, endometrial volume, sVI, sFI, sVFI, implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births(P>0.05). Conclusions: Manual acupuncture performed after oocyte aspiration and before transplantation improved the endometrial blood flow parametersVI, RI and VFI in women who underwent IVF-ET, instead of sVI, sFI and sVFI. Therefore, acupuncture might be beneficial in women undergoing IVF-ET by increasing endometrial blood flow and endometrial receptivity.(Registration No. ChiCTR2100053354)展开更多
The debate exists whether or not gonadotropin-releasing hormone（GnRH） analogs used in controlled ovarian hyperstimulation（COH） impair endometrial receptivity.Homeobox A11（Hoxa11）,Meis homeobox 1（Meis1）,cadheri...The debate exists whether or not gonadotropin-releasing hormone（GnRH） analogs used in controlled ovarian hyperstimulation（COH） impair endometrial receptivity.Homeobox A11（Hoxa11）,Meis homeobox 1（Meis1）,cadherin 1（Cdh1）,and catenin beta 1（Ctnnb1） are well known to be involved in successful implantation.In this study,the endometrial expression of Hoxa11,Meis1,Cdh1,and Ctnnb1 during the peri-implantation period was investigated in an in vitro fertilization（IVF） mouse model by real-time RT-PCR and Western blot to evaluate the relationship between Hoxa11,Meis1,Cdh1,and Ctnnb1 expression and the impact of the COH on endometrial receptivity.The mimic COH protocols included GnRH agonist plus human menopausal gonadotropin（HMG）（GnRH agonist group）,GnRH antagonist plus HMG（GnRH antagonist group）,and HMG alone（HMG group）.The expression levels of Hoxa11,Meis1,Cdh1,and Ctnnb1 mRNA and protein were decreased in all of the COH groups.The expression levels of Hoxa11 and Ctnnb1 were the lowest in the GnRH agonist group,and those of Meis1 and Cdh1 were lower in the GnRH analog groups than the HMG group.There were positive correlations between the expression of Hoxa11 and Ctnnb1,as well as the expression of Meis1 and Cdh1 among all the groups.In conclusion,the COH protocols,particularly with GnRH analogs,suppressed Hoxa11,Meis1,Ctnnb1 and Cdh1 expression,in mouse endometrium during the peri-implantation period.Our data reveal a novel molecular mechanism by which the COH protocols might impair endometrial receptivity.展开更多
Embryo implantation is a complicated physiological process tightly regulated by multiple biological molecules including growth factors.Transforming growth factor-betas(TGF-βs)and their most specific signal transducti...Embryo implantation is a complicated physiological process tightly regulated by multiple biological molecules including growth factors.Transforming growth factor-betas(TGF-βs)and their most specific signal transduction factors,Smads,are expressed in the endometrium during the window of implantation.Recent researches indicated that Smad dependent TGF-β signaling may play an important role in the process of embryo implantation.In this study,we measured the expression of TGF-β1,TGF-β receptor type I(TpRI),Smad3 and p-Smad3 in the endometrium of mice and observed their elevation on day 4,5 and 6 of pseudopregnancy.Then we administrated a specific Smad3 inhibitor(Sis3)into the uterine cavity of mice on day 3 of pregnancy.The results showed a reduction in insulin-like growth factor-1(IGFBP-1)expression and the decreased number of implanted embryo after the administration.In addition,Sis3 was found to reduce the IGFBP-1 secretion in decidualized endometrial stromal cells.Taken all together,our findings demonstrated that TGF-β/Smad3 signaling is involved in the process of embryo implantation.展开更多
Objective:The aim of this study was to determine the expression of Hoxa 10 in endometrium during the menstrual cycle and their response to sex steroids and HB-EGF.Methods:Forty endometrial samples from regularly cycli...Objective:The aim of this study was to determine the expression of Hoxa 10 in endometrium during the menstrual cycle and their response to sex steroids and HB-EGF.Methods:Forty endometrial samples from regularly cycling women were studied.The endometrial epithelial(EEC)and stromal(ESC)cells isolated by collagenase Ⅰ digestion and mechanical dissociation was cultured from every sample.The endometrial stromal cells(ESC)were incubated with 17-beta estradiol(10-8mol/L),medroxyprogesterone acetate(MPA)(10-6mol/L),RU486(10-8mol/L)or HB-EGF(10ng/ml)for 48 hours respectively.The expression of Hoxa10 mRNA was demonstrated by reverse transcription-polymerase chain reaction(RT-PCR).Result:Hoxa10 showed a regulated cycle phase-dependent expression pattern in stromal cells and epithelial cells.Hoxa10 expression dramatically increased during the midsecretory phase of the menstrual cycle,at the time of implantation.The expression of Hoxa10 in cultured endometrial stromal cells was stimulated by estrogen,progesterone and HB-EGF.Conclusion:The cycle phase-specific expression of Hoxa10 and up-regulated by sex steroids and HB-EGF suggests a tight regulation and establishing conditions necessary for implantation.展开更多
Objective:To observe the expression of endometrial homologous box gene A10(HOXA10),Integrinαvβ3 and leukemia suppressor factor(LIF)in peri-implantation mice,and to investigate the effect of controlled superovulation...Objective:To observe the expression of endometrial homologous box gene A10(HOXA10),Integrinαvβ3 and leukemia suppressor factor(LIF)in peri-implantation mice,and to investigate the effect of controlled superovulation(COH)on endometrial receptivity in mice.Methods:After COH model preparation and blastocyst transplantation,kunming pure-bred mature mice were randomly divided into natural blastocyst+natural pseudocyst group,COH blastocyst+natural pseudocyst group,natural blastocyst+COH pseudocyst group,and COH blastocyst+COH pseudocyst group.The pregnancy rate and average number of beds in each group were observed on day 6 of conception.Western blot and RT-PCR were used to detect the expression of HOXA10,Integrinααvβ3,LIF protein and mRNA in the endometria of mice on day 5 of conception.Results:The pregnancy rate and average number of beds in the COH group were lower than those in the natural receptor group.The expression of HOXA10,Integrinααvβ3 and LIF in endometrium was significantly lower than that of the natural receptor mice(P<0.01).Conclusion:Superovulation drugs down-regulate the expression of HOXA10,Integrinαvβ3 and LIF in endometrium during the implantation window,reduce endometrial receptivity,and lead to low clinical pregnancy rate.展开更多
The human endometrium and embryo both produce microRNAs(miRNAs),which are involved in various physiological activities.Accumulating evident suggested that endometrial miRNAs are regulated by steroid hormones that modu...The human endometrium and embryo both produce microRNAs(miRNAs),which are involved in various physiological activities.Accumulating evident suggested that endometrial miRNAs are regulated by steroid hormones that modulate endometrial functions,whereas embryo-derived miRNAs play vital roles in maternal–embryo communication.The aberrant expression of endometriumor embryo-derived miRNAs can cause early pregnancy and gestational disorders,including repeated implantation failure,recurrent miscarriage,and pathological conditions such as endometriosis.miRNAs are,therefore,ideal candidates for conducting clinicopathological tests.Potential diagnostic and prognostic tests using miRNAs are under development;however,the therapeutic applications of miRNAs in regulating gestational disorders require further investigation.展开更多
Background： At present, a diagnostic tool with high specificity for impaired endometrial receptivity, which may lead to implantation failure, remains to be developed. We aimed to assess the different endometrial micr...Background： At present, a diagnostic tool with high specificity for impaired endometrial receptivity, which may lead to implantation failure, remains to be developed. We aimed to assess the different endometrial microRNA （miRNA） signatures for impaired endometrial receptivity by microarray analysis. Methods： A total of 12 repeated implantation failure （RIF） patients and I0 infertile patients, who conceived and delivered after one embryo transfer attempt, were recruited as RIF and control groups, respectively. Endometrial specimens from the window of implantation （WOI） were collected from these two groups. MiRNA microarray was conducted on seven and five samples from the RIF and control groups, respectively. Comparative, functional, and network analyses were performed for the microarray results. Quantitative real-time polymerase chain reaction （PCR） was performed on other samples to validate the expression of specific miRNAs. Results： Compared with those in the control group, the expression levels of 105 miRNAs in the RIF group were found to be significantly up- or down-regulated （at least 2-fold） by microarray analysis. The most relevant miRNA functional sets of these dysregulated miRNAs were miR-30 family, human embryonic stern cell regulation, epithelial-mesenchymal transition, and miRNA tumor suppressors by tool for annotations ofmicroRNA analysis. Network regulatory analysis found 176 miRNA-mRNA interactions, and the top 3 core miRNAs were has-miR-4668-5p, has-miR-429, and has-miR-5088. Expression levels of the 18 selected miRNAs in new samples by real-time PCR were found to be regulated with the same trend, as the result ofmicroarray analysis. Conclusions： There is a significant different expression of certain miRNAs in the WOI endometrium for RIF patients. These miRNAs may contribute to impaired endometrial receptivity.展开更多
基金the Guangdong Medical Science and Technology Research Foundation(No.A2021345).
文摘Endometrial receptivity is an important factor that influences embryo implantation.Thus,it is important to identify an applicable approach to improve endometrial receptivity in women undergoing assisted reproductive technology.Recently,growing evidence has indicated that intrauterine platelet-rich plasma(PRP)infusion is an effective method to obtain a satisfactory reproductive outcome by increasing endometrial thickness and improving endometrial receptivity.Therefore,the present review aims to outline the possible mechanisms of PRP on endometrial receptivity and summarize the present literature on the effects of PRP therapy in improving endometrial receptivity.
文摘This study examined the impact of luteinized unruptured follicle （LUF） on endometrial receptivity. The menstrual cycle of 17 LUF patients （LUF group） and 13 ovulatory women （control group） was monitored by measuring LH level in urine and by ultrasonic examination. An endometrial biopsy at the sixth to tenth day after LH surge was taken in all the patients. The expressions of endometrial ER, PR and integrin ανβ3 were immunohistochemically determined. At the same time, the serum levels of E2 and P were detected by chemiluminescence. The results exhibited that （1） The mean serum P level in LUF group （7.32±2.56 ng/mL） was significantly lower than that in control group （11.17±3.17 ng/mL） （P0.01）. But there was no significant difference in the mean serum E2 levels between LUF group （179.35±81.60 pg/mL） and the control group （198.58±75.23 pg/mL） （P0.05）; （2） The mean expression intensities of ER, PR in endometrium of LUF group （183.86±2.43, 167.94±3.04） were significantly higher than those in control group （109.35±6.31, 105.98±4.07） （P0.01）; （3） The mean expression intensities of integrin ανβ3 in endomtrium of LUF patients （114.90±11.38） were significantly lower than those in control group （191.34±1.82） （P0.01）; （4） The change profile of integrin ανβ3 expression in the endometrium of LUF patients was in positive relation with serum P level （r=0.77, P0.01）, but bore no significant relationship with serum E2 level （r=0.01, P0.05）. It was concluded that the depression of serum P levels in LUF patients was closely related to the failure of the down-regulation of ER and PR, and the low expressions of integrin ανβ3 also suggested that the delayed implantation and the impaired endometrial receptivity had impact on embryonic implantation.
基金This study was supported by Beijing Nova Program(Z181100006218083)the Project of the National Natural Science Foundation of China(81874421)the Youth Project of the National Natural Science Foundation of China(81904240).
文摘Objective:Bushen Chengyun granule(BCG)is an empirical treatment for female infertility(FI)caused by low endometrial receptivity(LER)involving a poorly understood mechanism.In this study,network pharmacology was used to explore the potential therapeutic mechanism of BCG on FI caused by LER.Methods:The corresponding herb targets were obtained by conducting a search in the Traditional Chinese Medicine Systems Pharmacology Database and PubMed-reported literature.Disease targets were obtained from the following databases:Comparative Toxicogenomics Database,Human Phenotype Ontology,and Therapeutic Target Database.Treatments for LER using BCG have used target matching(BCG e LER target).Then,the predicted targets were uploaded to the Search Tool for the Retrieval of Interacting Genes/Proteins database for gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses.Furthermore,triptorelin acetate for injection t menotrophin t chorionic gonadotropin for injection were used to establish a mouse model of blastocyst implantation disorder and to evaluate the in vivo effect of BCG on blastocyst implantation.Results:Overall,156 bioactive chemical components and 1092 targets of BCG were identified.The results indicated that 482 biological processes(FDR<0.01)and 15 pathways(FDR<0.01)related to BCG participated in the complex treatment effects and were associated with the endocrine system,inflammatory responses,metabolism,apoptosis,ovulatory performance,and angiogenesis.Moreover,16 hub nodes of BCG including estrogen receptor(ESR1),estrogen receptor beta(ESR2),progesterone receptor,et al,were recognized as potential treatment targets and might help clarify the underlying therapeutic mechanisms of BCG for female infertility.BCG significantly increased the protein expressions of estrogen receptors and progesterone receptors.Conclusions:These findings reveal the potential therapeutic mechanism of BCG for female infertility involves low endometrial receptivity,which should be evaluated further.
文摘Objective To study the effect of single and low dose of RU486 on endometrial receptivity of healthy women. Methods A total of 5 healthy women were followed for one control and one treatment cycle. In the treatment cycle, a dose of 10 mg RU486 was administered on day luteinizing hormone (LH)-2. In both the control and treatment cycle, an endometrial biopsy was obtained on LH+7. These biopsies were assessed by immunohistochemical analysis to find the difference in expression of integrins and progesterone receptor (PR) between the control and treatment cycle. Results The treatment with RU486 increased the expression of α 1 and α 4 subunits of integrin in glandular epithelial cells, but did not influence β 3 subunit. Moreover, the normal down regulation of PR in epitherial cell nuclei was inhibited by 10 mg RU486. Conclusion Single dose of 10 mg RU486 impairs the establishment of endometrial receptivity on time.
基金Youth ChengGuang Science & Technology Foundation of Wuhan (20065004116- 15)Scientific Research Foundation of Hubei Province Health Department(No.JX2B11)
文摘Objective To establish the mice model of implantation dysfunction and to study the endometrial receptivity during implantation in implantation dysfunction mouse. Methods Sexually mature female virgin, Kunming mice were randomly assigned to the control group and the model group postcoitally. The model mice at 9 ： 00 AM on d 4 of pregnancy（d 4） were injected subcutaneously with mifepristone. All animals were sacrificed at 9 ：00 PM on d 4 and their uterine horns were examined for the presence of implanted embryos. Histopathology of uterine endometrium was observed by light-microscope. The endometrial expressions of estrogen receptor （ER） and progesterone receptor （PR） assessed by immunnohistochemical SP method. The endometrial expressions of ER mRNA and PR mRNA were assessed by semi-quantitative reverse transcriptase polymerase chain reaction （RT-PCR）. Results Compared with control group, implantation rates and average embryo num- ber significently decreased in model group, the development of endometrium was inhibited. In model group, absorbency and area rate of ER and PR in the gland and stroma were lower than those in control group （P〈0.05）. Expressions of ER mRNA and PR mRNA in model uterus were significantly lower than those in the control. Conclusion The endometrial receptivity and implantation decreased in mifepristoneinduced implantation dysfunction mouse.
基金Subject of the State Administration of Traditional Chinese Medicine(1199ws02)Project of Guangdong Provincial Bureau of Traditional Chinese Medicine(20181120)
文摘Objective: To systematically evaluate the efficacy and safety of Bushen Recipe combined with clomiphene compared with clomiphene in improving endometrial receptivity of polycystic ovary syndrome. Methods: The time limit is from the establishment of the database to January 2, 2020. A randomized controlled trial was conducted to compare the effects of Bushen Recipe combined with clomiphene and clomiphene on the endometrial receptivity of polycystic ovary syndrome (PCOS). Meta analysis was performed with RevMan5.3 software. Results: A total of 13 RCTS were included, with a total of 797 PCOS patients. The results of this meta-analysis show: there were statistically significant differences in the improvement of endometrial thickness [WMD=1.62,95%CI(1.22, 2.01), P <0.00001], endometrial type[RR=1.51,95%CI(1.28, 1.78), P <0.00001], uterine artery pulse index(PI) [WMD=-0.18,95%CI(-0.27, -0.09) , P <0.0001], uterine artery resistance index(RI)[WMD=-0.08,95%CI(-0.11, -0.05) , P <0.00001], pregnancy rate [RR=2.18,95%CI(1.55, 3.05), P <0.00001], TCM syndrome score[WMD=-6.97,95%CI(-8.97, -4.97) , P <0.00001], effective rate [RR=1.25, 95%CI (1.13, 1.37), P < 0.00001]. Conclusion: Compared with clomiphene alone, Bushen Recipe combined with clomiphene can effectively increase the thickness of endometrium and improve the type of endometrium, promote the blood perfusion of endometrium, improve the pregnancy rate, improve the clinical symptoms, reduce the TCM syndrome score, improve the total efficiency of treatment, with high clinical application value.
基金supported by grants from the Sanming Project of Medicine in Shenzhen,China(SZSM201612083 to W.S.B.Y.)Shenzhen Key Medical Discipline(SZXK2020089)+2 种基金General Research Fund,Research Grants Council,Hong Kong(06173976 and 17120720 to K.F.L.)Health and Medical Research Fund,Hong Kong(06173976 to K.F.L.)Internal Research Funding from the Department of Obstetrics and Gynecology at the University of Hong Kong.
文摘Successful implantation requires concerted interactions during the apposition,adhesion,and invasion of the embryo into a receptive endometrium.However,the embryo implantation rate for assisted reproduction remains low despite the transfer of good quality embryos.Changes in endometrial transcriptomics,proteomics,lipidomics,and even microbiota all play important roles in embryo implantation.Specifically,the expression of steroid hormone-regulated adhesive and anti-adhesive molecules during the embryo implantation window is becoming an area of increasingly intense research.This review(a)summarizes the different molecules expressed in the receptive endometrium and(b)proposes the use of surface protein markers to predict pregnancy outcomes from assisted reproduction.
基金funded by the National Natural Science Foundation of China(81473721,81273789)。
文摘Background: Rhizoma drynariae is a traditional Chinese medicine used in orthopedics and traumatology, but its effect on endometrial receptivity remains unknown. Aims and Objectives: To observe effect of Rhizoma drynariae and its main components on endometrial receptivity in a mus model of dysfunctional embryo implantation. Materials and Methods: Mus models were established by the Gn RHa+HMG+HCG method. Normal mus receiving saline were used as controls and the remaining six groups were: model receiving saline, progynova, aspirin, Rhizoma drynariae, osteopractic total flavone, and naringin. Pinopodes in uterine endometrium were examined by scanning electron microscopy. Stem cell factor(SCF) m RNA expressions was determined by real-time RT-PCR, and estrogen receptor α(ERα), progesterone receptor(PR) by immunohistochemistry. Results: In the model group, surface morphology of endometrium was heterogeneous, without obvious pinopodes. In the Rhizoma drynaria and progynova groups, pinopodes were abundant. Compared with the blank group, model group had lower levels of SCF(-47%), ERα(-63%) and PR(-50%)(all P<0.05). In comparison, Rhizoma drynariae group had higher levels of SCF(+73%), ERα(+118%) and PR(+101%)(all P<0.01). The individual main components of Rhizoma drynariae had variable efficacy. Conclusion: Rhizoma drynariae could improve endometrial receptivity of mouse models of dysfunctional embryo implantation as shown by increased numbers of pinopodes and higher levers of SCF, ERα, PR compared with the model group.
基金Supported by Natural Science Foundation of China Grants (No:90209009)National Basic 973 Research Grant (2006CB504502)
文摘Objective To observe acupuncture effects on endometrial receptivity of the rats with polycystic ovary syndrome （PCOS） treated by ovarian stimulation with Clomiphene to explore its mechanisms. Methods eGOS rat model was experimentally induced by subcutaneous injection of oil solution of dehydroepiandrosterone （DHEA） in immature （24-day-old） female rats for continuous 20 days. The same dose of oil was given for an equivalent length of time to animals in a control group （Group Con）. The rats with PCOS were randomly divided into a model group （group M）, a Clomiphene treatment group （group C）, a Clomiphene plus acupuncture group （group C＋ A）. The treatments were given for 5 days since 80 days after birth. Half of the rats were killed by decapitation after treatment finished, and the serum, uteri and endometria were obtained. The other half mated with male rats, and they were killed at the 8th day of pregnancy. We observed the implantation number and condition of pregnant uteri. Results Compared with group C, the animals in group C＋A had higher implantation rate and more average implanted embryos （P〈0. 01 ）, higher serum estradiol （E2） level （P〈0.01 ）, better development of endometrium, and increased mRNA and protein expressions of molecular markers of endometrial receptivity （P〈0.01）, which were closer to those in the control group. Conclusion Acupuncture could improve poor endometrial receptivity of PCOS rats with ovarian stimulation by citrated Clomiphene and promote implantation. The effects may be related with its up-regulation of serum E2 level, mRNA and protein expressions of molecular markers of endometrial receptivity.
基金Supported by Fujian Natural Science(No.2017J01237)Science and Technology Innovation Start-up Fund of Fujian Women and Children Health Care Hospital(Youth Science,No.Women and Children YCXQ 18-10)+1 种基金Key Youth Projects of Fujian Health Commission(No.2017-ZQN-19)Fujian Science and Technology Project(No.201910024)。
文摘Objective:To observe the effect of the combined therapy of electroacupuncture(EA) and ginger-isolated moxibustion on endometrial receptivity in the patients with polycystic ovarian syndrome(PCOS).Methods:A total of 70 subjects of PCOS were randomized into two groups,35 cases in each one.In the western medication group,letrozole and human chorionic gonadotropin(HCG) were administered.In the combined therapy group,on the base of the treatment as the western medication group,the artificial cycle therapy with EA and ginger-isolated moxibustion was provided.The treatment duration was 3 menstrual cycles in two groups.After treated for 3 menstrual cycles,the symptom score of traditional Chinese medicine(TCM),endometrial thickness,the number of ovulation cycle,endometrial morphology,bilateral uterine artery pulsatility index(PI),resistance index(RI),the sum of peak systolic velocity/end diastolic velocity(S/D) and pregnancy were compared in the patients between two groups.Results:(1) After treatment,the endometrial thickness was better(0.21 ± 0.13 vs 0.14 ± 0.08,P <0.01),TCM symptom score reducing range was larger(5.00 ± 2.24 vs 0.52 ± 1.66,P <0.01),the reducing degrees of bilateral uterine artery PI,RI and S/D sum were better(0.62 ± 0.26 vs 0.04 ± 0.15,0.08± 0.05 vs0.01±0.05,0.61±0.33 vs 0.07±0.17,0.11±0.05 vs 0.01 ± 0.05,4.80±1.14 vs 0.15 ± 0.89,all P <0.01) in the combined therapy group respectively as compared with the western medication group.After treatment,the number of ovulation cycle and the proportion of A+B type of endometrial morphological were higher in the combined therapy group(2.09 ± 0.78 vs 1.27 ± 0.84,87.5% vs 60.61%,P <0.01,P <0.05) as compared with the western medication group respectively.(2) The clinical pregnancy rate was56.25% in the combined therapy group,better than 30.30% in the western medication group(P <0.05).The early abortion rate was 10.53% in the combined therapy group,lower than 50.00% in the western medication group(P <0.05).Conclusion:The combined treatment of electroacupuncture and ginger-isolated moxibustion with western medication effectively improves endometrial receptivity,increases clinical pregnancy rate and reduces early abortion rate in the patients with PCOS.
基金supported by the National Natural Science Foundation of China (81490742, 82001537)the Fundamental Research Funds for the Central Universities (2021FZZX003-02-18)the National Key Research and Development Program of China (2018YFC1004402)。
文摘Diabetes is a complex metabolic disorder which can adversely affect reproductive function. SGK1 is found to be up-regulated in multiple tissues of diabetic patients. However, the effects of diabetes on endometrial SGK1 expression and endometrial receptivity remain unknown. In this study, we established a streptozotocin-induced diabetic mouse model and observed reduced implantation sites, retarded development of pinopodes, increased SGK1, and aberrant expression of LIF and MUC1 in the endometrial epithelium. We injected the uterine lumen of normal mice with high-glucose solution and cultured endometrial cells in high-glucose medium to mimic intrauterine hyperglycemia. Both studies provided compelling evidence that hyperglycemia could lead to diminished embryo implantation and dysregulated SGK1, LIF and MUC1. Additionally, through over-expression of SGK1 in vivo and in vitro, we found that enhanced SGK1 also decreased LIF expression, increased MUC1 expression, and attenuated embryo implantation rate. We further identified that hyperglycemia-activated SMAD2/3 might be responsible for the enhancement of SGK1 and verified directly the interaction between SMAD3 and corresponding SMAD binding elements within SGK1 promoter. Taken together, our study confirmed the association between diabetes-related hyperglycemia and endometrial receptivity defects. Hyperglycemia-induced SGK1 has a tremendous role in this pathological process, rendering it as an attractive therapeutic target for diabetes-related reproductive disorders.
文摘Objective To evaluate endometrial and subendometrial blood flows measured by vaginal color Doppler ultrasound as a predicator of endometrial receptivity in women undergoing IVF treatment. Methods A total of 119 infertile patients undergoing the first IVF/ICSI-ET cycle were recruited. Three groups were divided according to a color Doppler ultrasound examination performed on the day of hCG injection. Group A, endometrial and subendometrial blood flows were 2 branches and below; group B, endometrial and subendometrial blood flows were between 3 and 4 branches; group C, endometrial and subendometrial blood flows were 5 branches and above. Patients were transferred 1-3 embryos each. Demographic data, ovarian responses, endometrial thickness, PI, RI, development of embryo and IVF result among groups were compared. Results Demographic data, ovarian responses, endometrial thickness, PI, RI and development of embryo among groups have no significant difference. The pregnancy rate of group A was significantly lower than that of group B （P〈0.05） and group C （P〈0.01）. The implantation rate of group A was significantly lower than than of group C （P〈0.01）. There was no significant difference of the rate of pregnancy and implantation between group B and group C （P〉0.05）. Conclusion Endometrial and subendometrial blood flows measured by vaginal color Doppler ultrasound is a good predicator of pregnancy during IVF treatment. A good endometrial and subendometrial blood flows is benefit for the result of IVF.
基金supported by grants from the Sanming Project of Medicine in Shenzhen,China(SZSM201612083 to W.S.-B.Y.)Shenzhen Key Medical Discipline(SZXK2020089)+1 种基金General Research Fund,Research Grants Council,Hong Kong(17120720 to K.-F.L.)internal research funding from the Department of Obstetrics and Gynaecology,the University of Hong Kong.
文摘This review summarizes the drugs and chemicals that may modulate embryo implantation.Non-hormonal molecules,including aspirin,improved endometrial blood flow,while low molecular weight heparin,vitamin E,sildenafil,and atosiban modulated the expression of endometrial genes.Hormonal factors,including human chorionic gonadotropin and growth hormones,can regulate the expression of endometrial receptivity markers.Other immunomodulatory molecules,including granulocyte colony-stimulating factor,peripheral blood mononuclear cells,autologous platelet-rich plasma,and intralipid and intravenous immunoglobulins,may improve implantation rate by modulating endometrial immune functions.Medicinal extracts of the Chinese herbs Paeonia lactiflora and Perilla frutescens increased the expression of leukemia inhibitory factors in endometrial epithelial cells.Recently,the use of the commercially available Library of Pharmacologically Active Compounds with a high-throughput screening method has provided an approach to screen for compounds that may potentially enhance or suppress embryo implantation.Whether these biomedical findings translate into clinical effects that enhance or suppress embryo implantation requires further investigation.
基金Supported by National Natural Science Foundation of China (No. 81202827)。
文摘Objective: To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional(3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer(IVF-ET). Methods: Seventy patients undergoing IVF-ET were equally randomized into traditional or sham acupuncture treatment group for totally 4 days(from the day of oocyte aspiration to the day of embryo transfer) of treatment by random envelope method at the Reproductive Medicine Center and Outpatient Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology from January 2013 to December 2015. Patients in the traditional acupuncture group accepted traditional acupuncture methods with manual acupuncture, and Zhongji(CV3), Qihai(CV 6), Sanyinjiao(SP6), Taichong(LR 3), Tianshu(ST 25), Guilai(ST 29) and Zusanli(ST 36) were chosen. Patients at the sham acupuncture group accepted shallow acupuncture methods at 4 non-meridian points at each shoulder and upper arm. Outcome measures included endometrial ultrasonic indices such as vascularization index(VI), flow index(FI) and vascularization flow index(VFI), endometrial thickness and volume, subendometrial VI(sVI), subendometrial FI(sFI), subendometrial VFI(sVFI), implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births. Results: Finally, 34 patients in the traditional acupuncture group and 35 in the sham acupuncture group completed this trial. VI, FI and VFI of the traditional acupuncture group were significantly higher than those in the sham acupuncture group(P<0.05). No significant differences were found in endometrial thickness, endometrial volume, sVI, sFI, sVFI, implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births(P>0.05). Conclusions: Manual acupuncture performed after oocyte aspiration and before transplantation improved the endometrial blood flow parametersVI, RI and VFI in women who underwent IVF-ET, instead of sVI, sFI and sVFI. Therefore, acupuncture might be beneficial in women undergoing IVF-ET by increasing endometrial blood flow and endometrial receptivity.(Registration No. ChiCTR2100053354)
基金supported by a grant from the Major State Basic Research Development Program of China (973 Program)(No. 2007-CB948100)
文摘The debate exists whether or not gonadotropin-releasing hormone（GnRH） analogs used in controlled ovarian hyperstimulation（COH） impair endometrial receptivity.Homeobox A11（Hoxa11）,Meis homeobox 1（Meis1）,cadherin 1（Cdh1）,and catenin beta 1（Ctnnb1） are well known to be involved in successful implantation.In this study,the endometrial expression of Hoxa11,Meis1,Cdh1,and Ctnnb1 during the peri-implantation period was investigated in an in vitro fertilization（IVF） mouse model by real-time RT-PCR and Western blot to evaluate the relationship between Hoxa11,Meis1,Cdh1,and Ctnnb1 expression and the impact of the COH on endometrial receptivity.The mimic COH protocols included GnRH agonist plus human menopausal gonadotropin（HMG）（GnRH agonist group）,GnRH antagonist plus HMG（GnRH antagonist group）,and HMG alone（HMG group）.The expression levels of Hoxa11,Meis1,Cdh1,and Ctnnb1 mRNA and protein were decreased in all of the COH groups.The expression levels of Hoxa11 and Ctnnb1 were the lowest in the GnRH agonist group,and those of Meis1 and Cdh1 were lower in the GnRH analog groups than the HMG group.There were positive correlations between the expression of Hoxa11 and Ctnnb1,as well as the expression of Meis1 and Cdh1 among all the groups.In conclusion,the COH protocols,particularly with GnRH analogs,suppressed Hoxa11,Meis1,Ctnnb1 and Cdh1 expression,in mouse endometrium during the peri-implantation period.Our data reveal a novel molecular mechanism by which the COH protocols might impair endometrial receptivity.
基金the National Natural Science Foundation of China(No.81701450).
文摘Embryo implantation is a complicated physiological process tightly regulated by multiple biological molecules including growth factors.Transforming growth factor-betas(TGF-βs)and their most specific signal transduction factors,Smads,are expressed in the endometrium during the window of implantation.Recent researches indicated that Smad dependent TGF-β signaling may play an important role in the process of embryo implantation.In this study,we measured the expression of TGF-β1,TGF-β receptor type I(TpRI),Smad3 and p-Smad3 in the endometrium of mice and observed their elevation on day 4,5 and 6 of pseudopregnancy.Then we administrated a specific Smad3 inhibitor(Sis3)into the uterine cavity of mice on day 3 of pregnancy.The results showed a reduction in insulin-like growth factor-1(IGFBP-1)expression and the decreased number of implanted embryo after the administration.In addition,Sis3 was found to reduce the IGFBP-1 secretion in decidualized endometrial stromal cells.Taken all together,our findings demonstrated that TGF-β/Smad3 signaling is involved in the process of embryo implantation.
文摘Objective:The aim of this study was to determine the expression of Hoxa 10 in endometrium during the menstrual cycle and their response to sex steroids and HB-EGF.Methods:Forty endometrial samples from regularly cycling women were studied.The endometrial epithelial(EEC)and stromal(ESC)cells isolated by collagenase Ⅰ digestion and mechanical dissociation was cultured from every sample.The endometrial stromal cells(ESC)were incubated with 17-beta estradiol(10-8mol/L),medroxyprogesterone acetate(MPA)(10-6mol/L),RU486(10-8mol/L)or HB-EGF(10ng/ml)for 48 hours respectively.The expression of Hoxa10 mRNA was demonstrated by reverse transcription-polymerase chain reaction(RT-PCR).Result:Hoxa10 showed a regulated cycle phase-dependent expression pattern in stromal cells and epithelial cells.Hoxa10 expression dramatically increased during the midsecretory phase of the menstrual cycle,at the time of implantation.The expression of Hoxa10 in cultured endometrial stromal cells was stimulated by estrogen,progesterone and HB-EGF.Conclusion:The cycle phase-specific expression of Hoxa10 and up-regulated by sex steroids and HB-EGF suggests a tight regulation and establishing conditions necessary for implantation.
基金General program of national natural science foundation of China(No.81674060)Promotion project for special subjects of Jianghan University(No.03100041)。
文摘Objective:To observe the expression of endometrial homologous box gene A10(HOXA10),Integrinαvβ3 and leukemia suppressor factor(LIF)in peri-implantation mice,and to investigate the effect of controlled superovulation(COH)on endometrial receptivity in mice.Methods:After COH model preparation and blastocyst transplantation,kunming pure-bred mature mice were randomly divided into natural blastocyst+natural pseudocyst group,COH blastocyst+natural pseudocyst group,natural blastocyst+COH pseudocyst group,and COH blastocyst+COH pseudocyst group.The pregnancy rate and average number of beds in each group were observed on day 6 of conception.Western blot and RT-PCR were used to detect the expression of HOXA10,Integrinααvβ3,LIF protein and mRNA in the endometria of mice on day 5 of conception.Results:The pregnancy rate and average number of beds in the COH group were lower than those in the natural receptor group.The expression of HOXA10,Integrinααvβ3 and LIF in endometrium was significantly lower than that of the natural receptor mice(P<0.01).Conclusion:Superovulation drugs down-regulate the expression of HOXA10,Integrinαvβ3 and LIF in endometrium during the implantation window,reduce endometrial receptivity,and lead to low clinical pregnancy rate.
基金the RGC General Research Fund(17120720)Health and Medical Research Fund,Hong Kong(08192326)Conference and Research Committee grant from the University of Hong Kong to K.F.L.
文摘The human endometrium and embryo both produce microRNAs(miRNAs),which are involved in various physiological activities.Accumulating evident suggested that endometrial miRNAs are regulated by steroid hormones that modulate endometrial functions,whereas embryo-derived miRNAs play vital roles in maternal–embryo communication.The aberrant expression of endometriumor embryo-derived miRNAs can cause early pregnancy and gestational disorders,including repeated implantation failure,recurrent miscarriage,and pathological conditions such as endometriosis.miRNAs are,therefore,ideal candidates for conducting clinicopathological tests.Potential diagnostic and prognostic tests using miRNAs are under development;however,the therapeutic applications of miRNAs in regulating gestational disorders require further investigation.
文摘Background： At present, a diagnostic tool with high specificity for impaired endometrial receptivity, which may lead to implantation failure, remains to be developed. We aimed to assess the different endometrial microRNA （miRNA） signatures for impaired endometrial receptivity by microarray analysis. Methods： A total of 12 repeated implantation failure （RIF） patients and I0 infertile patients, who conceived and delivered after one embryo transfer attempt, were recruited as RIF and control groups, respectively. Endometrial specimens from the window of implantation （WOI） were collected from these two groups. MiRNA microarray was conducted on seven and five samples from the RIF and control groups, respectively. Comparative, functional, and network analyses were performed for the microarray results. Quantitative real-time polymerase chain reaction （PCR） was performed on other samples to validate the expression of specific miRNAs. Results： Compared with those in the control group, the expression levels of 105 miRNAs in the RIF group were found to be significantly up- or down-regulated （at least 2-fold） by microarray analysis. The most relevant miRNA functional sets of these dysregulated miRNAs were miR-30 family, human embryonic stern cell regulation, epithelial-mesenchymal transition, and miRNA tumor suppressors by tool for annotations ofmicroRNA analysis. Network regulatory analysis found 176 miRNA-mRNA interactions, and the top 3 core miRNAs were has-miR-4668-5p, has-miR-429, and has-miR-5088. Expression levels of the 18 selected miRNAs in new samples by real-time PCR were found to be regulated with the same trend, as the result ofmicroarray analysis. Conclusions： There is a significant different expression of certain miRNAs in the WOI endometrium for RIF patients. These miRNAs may contribute to impaired endometrial receptivity.
