In order to assess the impact of mRNA degradation on steady state levels of follicle stimulating hormone receptor (FSHR) mRNA and on regulation of FSHR gene expression, the stability and half life of FSHR mRNA were de...In order to assess the impact of mRNA degradation on steady state levels of follicle stimulating hormone receptor (FSHR) mRNA and on regulation of FSHR gene expression, the stability and half life of FSHR mRNA were determined in transfected cells expressing recombinant FSHR. Time dependent changes in FSHR mRNA content were determined by nuclease protection solution hybridization assay (NPA) or by qualitative reverse transcription competitive polymerase chain reaction (RT PCR) in cultured hFSHR YI cells, cell lines stably transfected with a human FSHR cDNA. FSHR mRNA content remained constant during 8 h control incubations of hFSHR Y1 cells (NPA, 2.9±0.3 μg/mg RNA; RT PCR, 2.7±0.3 μg/mg RNA). Actinomycin D (ActD, 5 μg/ml) inhibited mRNA synthesis, as assessed by incorporation of uridine into total RNA, by 90 % within 1 h in hFSHR Y1 cells. No effect of ActD on cellular morphology or viability was observed. ActD caused a time dependent decrease in FSHR mRNA content in hFSHR Y1 cell lines with a lag time of 1 h. There were no significant differences in the rate of FSHR mRNA degradation between the two methods of mRNA quantification. The half life of hFSHR mRNA was 3.6±0.2 h by NPA and 3.1±0.1 h by RT PCR. The results indicated that degradation of mRNA was an important process in maintenance of steady state expression of the FSHR gene in cells stably expressing recombinant receptor.展开更多
Objective:This study is to investigate the effect of different single-nucleotide polymorphisms of follicle-stimulating hormone receptor(FSHR)gene on gonadotropin(Gn)administration dosage during controlled ovarian hype...Objective:This study is to investigate the effect of different single-nucleotide polymorphisms of follicle-stimulating hormone receptor(FSHR)gene on gonadotropin(Gn)administration dosage during controlled ovarian hyperstimulation(COH)protocol of in vitro fertilization and embryo transfer.Methods:This retrospective study included 184 Chinese infertile women in Center for Reproduction and Genetics of Suzhou Municipal Hospital from June 2012 to 2014.All of the enrolled patients were homogeneous in some basal characteristics,and they all met the eligibility criteria.Blood tests were conducted on day 3 of menstrual cycle or the day of human chorionic gonadotropin administration for hormonal profile analysis and DNA extraction.DNA sequencing was performed for polymorphism analysis.The participants were classified into threonine(Thr)/Thr,Thr/alanine(Ala),and Ala/Ala groups according to genotype at position 307,and asparagine/asparagine(Asn/Asn),Asn/serine(Ser),and Ser/Ser groups according to genotype at position 680.Logistic regression and correlation analyses were performed to identify the effect of these two polymorphisms on Gn consumption.Results:The frequency of Thr307Ala and Asn680Ser distribution was consistent with Hardy-Weinberg equilibrium(P>0.05).No significant difference was found in age,basal hormone levels for different genotype groups.Logistic regression analysis results revealed that patients with Ser680Ser genotype have a higher risk of requiring a high dose of Gn compared with patients with Asn680Asn genotype,while polymorphism of Thr307 Ala has no such effect.Conclusion:This study suggested that FSHR genotype Asn680Ser would be helpful in determining the dosage of Gn in COH;patients with Ser680Ser genotype may require higher dose of Gn.展开更多
Health status of donor cows during superovulation is important to ensure optimal embryo quality at time of collection. Because nutritional and metabolic status impact embryo quality some form of nutritional supplement...Health status of donor cows during superovulation is important to ensure optimal embryo quality at time of collection. Because nutritional and metabolic status impact embryo quality some form of nutritional supplementation is often provided before and during superovulation. OmniGen-AF® (OG) feeding has been shown to assist in the maintenance of animal health through regulation of metabolic status and balance and supporting aspects of immune function. We observed feeding donor cows OG decreased percent degenerate embryos recovered following superovulation increased serum progesterone concentration and improved in vitro embryo development. Evaluation of OG feeding on markers of metabolic function and inflammatory and immune function in beef cattle embryo donors are reported here. Similarly, cow metabolic and inflammatory response with repeated superovulation protocols is not known. Biomarkers to monitor and evaluate cow health during superovulation may provide management options to improve embryo recovery and quality. Twenty-four Angus cross-bred cattle were randomly assigned to four treatment groups, fed 0 or 56 g/hd/day for 49 days and superovulated with 200 or 400 mg Folltropin V (FSH). Blood was collected weekly for analyses. The protocol was repeated on all cows 90</span><span style="font-family:""> </span><span style="font-family:Verdana;">-</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">120 d later with cows reassigned to their original groups. No differences (</span><i><span style="font-family:Verdana;">P</span></i><span style="font-family:Verdana;"> > 0.10) were observed due to OG feeding or FSH dose on metabolic and inflammatory markers. Replicate exerted a significant effect where serum concentration of albumin, IL1β, IL6, PGE</span><sub><span style="font-family:Verdana;">2</span></sub><span style="font-family:Verdana;"> and leptin were lower (</span><i><span style="font-family:Verdana;">P</span></i><span style="font-family:Verdana;"> < 0.05) in Replicate 1 compared to 2. There was also a similar pattern of change in several of the metabolic and inflammatory markers during the superovulation protocol where concentrations were higher at the time of estrus and ovulation. Taken together, physiologic changes during the estrous cycle and the number of superovulation protocols can modulate metabolic markers and inflammatory response.展开更多
Embryo quality is crucial when selecting embryos for transfer. Variation in quality may be attributed to poor oocytes, semen, stress, inflammation, and potential immune system dysregulation. OmniGen-AF<sup>&...Embryo quality is crucial when selecting embryos for transfer. Variation in quality may be attributed to poor oocytes, semen, stress, inflammation, and potential immune system dysregulation. OmniGen-AF<sup>®</sup> (OG) feeding supports immune system function and animal health. Our laboratory recently reported lower percent degenerate embryos recovered and increased plasma progesterone in beef cattle donors fed OG during superovulation. <i></span><i><span style="font-family:Verdana;">In vitro</span></i><span style="font-family:Verdana;"></i> development of embryos recovered from donor cows fed OG prior to collection is presented here. Embryos were recovered from 24 beef cows assigned to four treatment groups: 0 g OG/hd/d and 200 mg Folltropin<sup>®</sup>-V (FSH) (0/200);0 g OG/hd/d and 400 mg FSH (0/400), 56 g OG/hd/d, 200 mg FSH (56/200) and 56 g OG/hd/d and 400 mg FSH (56/400). Good to excellent quality early blastocysts were cultured for 8 d. and development through hatching, embryonic volume and plasminogen activator (PA) production were quantified. The complete protocol was repeated 90 - 120 d later as Replicate 2. Optimal development was observed by embryos recovered from 0/200 cows where percent blastocysts hatching was greater </span><span style="font-family:Verdana;">(</span><span style="font-family:Verdana;"><i></span><i><span style="font-family:Verdana;">P</span></i><span style="font-family:Verdana;"></i></span><span style="font-family:Verdana;"> < 0.05)</span> <span style="font-family:Verdana;">compared to 56/200 and 0/400 cows and embryonic volume was greatest (</span><span style="font-family:Verdana;"><i></span><i><span style="font-family:Verdana;">P</span></i><span style="font-family:Verdana;"></i></span><span style="font-family:Verdana;"> < 0.05) in Replicate 1. However, percent blastocysts hatching from 0/200 cows</span><span style="font-family:Verdana;"> was similar (<i></span><i><span style="font-family:Verdana;">P</span></i><span style="font-family:Verdana;"></i> > 0.10) to 56/400 cows and embryos recovered from 56/400 cows in Replicate 1 produced more (<i></span><i><span style="font-family:Verdana;">P</span></i><span style="font-family:Verdana;"></i> < 0.05) PA compared to all other groups. For cows superovulated with the standard 400-mg FSH dose, feeding OG supported </span><i><span style="font-family:Verdana;">in vitro</span></i><span style="font-family:Verdana;"> embryo development similar to that observed for 0/200 cows.展开更多
In a growing follicle,the survival and maturation of the oocyte largely depend on support from somatic cells to facilitate FSH-induced mutual signaling and chemical communication.Although apoptosis and autophagy in so...In a growing follicle,the survival and maturation of the oocyte largely depend on support from somatic cells to facilitate FSH-induced mutual signaling and chemical communication.Although apoptosis and autophagy in somatic cells are involved in the process of FSH-induced follicular development,the underlying mechanisms require substantial study.According to our study,along with FSH-induced antral follicles(AFs)formation,both lysine-specific demethylase 1(LSD1)protein levels and autophagy increased simultaneously in granulosa cells(GCs)in a time-dependent manner,we therefore evaluated the importance of LSD upon facilitating the formation of AFs correlated to autophagy in GCs.Conditional knockout of Lsdl in GCs resulted in significantly decreased AF number and subfertility in females,accompanied by marked suppression of the autophagy in GCs.On the one hand,depletion of Lsd1 resulted in accumulation of Wilms tumor 1 homolog(WT1),at both the protein and mRNA levels.WT1 prevented the expression of FSH receptor(Fshr)in GCs and thus reduced the responsiveness of the secondary follicles to FSH induction.On the other hand,depletion of LSD1 resulted in suppressed level of autophagy by upregulation of ATG16L2 in GCs.We finally approved that LSD1 contributed to these sequential activities in GCs through its H3K4me2 demethylase activity.Therefore,the importance of LSD1 in GCs is attributable to its roles in both accelerating autophagy and suppressing WT1 expression to ensure the responsiveness of GCs to FSH during AFs formation.展开更多
Alzheimer’s disease(AD)is the most common type of dementia.Almost two-thirds of patients with AD are female.The reason for the higher susceptibility to AD onset in women is unclear.However,hormone changes during the ...Alzheimer’s disease(AD)is the most common type of dementia.Almost two-thirds of patients with AD are female.The reason for the higher susceptibility to AD onset in women is unclear.However,hormone changes during the menopausal transition are known to be associated with AD.Most recently,we reported that follicle-stimulating hormone(FSH)promotes AD pathology and enhances cognitive dysfunctions via activating the CCAAT-enhancer-binding protein(C/EBPβ)/asparagine endopeptidase(AEP)pathway.This review summarizes our current understanding of the crucial role of the C/EBPβ/AEP pathway in driving AD pathogenesis by cleaving multiple critical AD players,including APP and Tau,explaining the roles and the mechanisms of FSH in increasing the susceptibility to AD in postmenopausal females.The FSH-C/EBPβ/AEP pathway may serve as a novel therapeutic target for the treatment of AD.展开更多
OBJECTIVE:To assess the efficacy of acupoint therapy combined with spine pinching in patients with menopausal syndrome.METHODS:This is a parallel,randomized,controlled,investigator-blinded trial.A total of 132 partici...OBJECTIVE:To assess the efficacy of acupoint therapy combined with spine pinching in patients with menopausal syndrome.METHODS:This is a parallel,randomized,controlled,investigator-blinded trial.A total of 132 participants were randomly assigned to receive either acupoint therapy combined with spine pinching(intervention group)or tibolone therapy alone(control group).The intervention group received acupoint therapy combined with spine pinching three times per week for 4 weeks.The control group received 2.5 mg of tibolone once daily for 4 weeks.The primary outcome was the improved Kupperman score.The WHO quality of life scale was also used.The secondary aim was to identify those who would benefit from acupoint therapy combined with spine pinching based on the levels of follicle stimulating hormone(FSH)and luteinizing hormone(LH).RESULTS:In the intervention group,the improved Kupperman score was significantly decreased after treatment compared with before treatment.However,there were no differences between the intervention and control groups for any outcome.Changes in the physiology score presented negative outcomes in patients with a low FSH level with increasing body mass index(BMI)(P=0.0).In contrast,changes in the physiology score presented positive outcomes in patients with a moderate LH level with increasing BMI(P=0.0).The mean change in the physiology score of patients with a low FSH level and a BMI of≥25.7 kg/m2 was-7.17(range-10.94 to-3.40)after adjustments for age and disease duration.CONCLUSION:Acupoint therapy combined with spine pinching is effective in treating menopausal syndrome,especially in women with a moderate LH level.However,patients with a low FSH level had a negative outcome after acupoint therapy combined with spine pinching.In addition,patients with a BMI of>25.7 kg/m2 had a negative outcome after the intervention,regardless of hormone levels.展开更多
基金Hubei Family PlanningL ommision Foundation and Hubei Science and TechnologyDepartment Foundation
文摘In order to assess the impact of mRNA degradation on steady state levels of follicle stimulating hormone receptor (FSHR) mRNA and on regulation of FSHR gene expression, the stability and half life of FSHR mRNA were determined in transfected cells expressing recombinant FSHR. Time dependent changes in FSHR mRNA content were determined by nuclease protection solution hybridization assay (NPA) or by qualitative reverse transcription competitive polymerase chain reaction (RT PCR) in cultured hFSHR YI cells, cell lines stably transfected with a human FSHR cDNA. FSHR mRNA content remained constant during 8 h control incubations of hFSHR Y1 cells (NPA, 2.9±0.3 μg/mg RNA; RT PCR, 2.7±0.3 μg/mg RNA). Actinomycin D (ActD, 5 μg/ml) inhibited mRNA synthesis, as assessed by incorporation of uridine into total RNA, by 90 % within 1 h in hFSHR Y1 cells. No effect of ActD on cellular morphology or viability was observed. ActD caused a time dependent decrease in FSHR mRNA content in hFSHR Y1 cell lines with a lag time of 1 h. There were no significant differences in the rate of FSHR mRNA degradation between the two methods of mRNA quantification. The half life of hFSHR mRNA was 3.6±0.2 h by NPA and 3.1±0.1 h by RT PCR. The results indicated that degradation of mRNA was an important process in maintenance of steady state expression of the FSHR gene in cells stably expressing recombinant receptor.
基金financially supported by Province Funds of Zhejiang University Medical School Key Laboratory(2012-RG/GH-0006)Jiangsu Key talents of maternal and child health(FRC2017250)+1 种基金Clinical research special funds of Wu Jieping Foundation,China(320.6755.15027)Suzhou Key Medical Center,(SZZX201505).
文摘Objective:This study is to investigate the effect of different single-nucleotide polymorphisms of follicle-stimulating hormone receptor(FSHR)gene on gonadotropin(Gn)administration dosage during controlled ovarian hyperstimulation(COH)protocol of in vitro fertilization and embryo transfer.Methods:This retrospective study included 184 Chinese infertile women in Center for Reproduction and Genetics of Suzhou Municipal Hospital from June 2012 to 2014.All of the enrolled patients were homogeneous in some basal characteristics,and they all met the eligibility criteria.Blood tests were conducted on day 3 of menstrual cycle or the day of human chorionic gonadotropin administration for hormonal profile analysis and DNA extraction.DNA sequencing was performed for polymorphism analysis.The participants were classified into threonine(Thr)/Thr,Thr/alanine(Ala),and Ala/Ala groups according to genotype at position 307,and asparagine/asparagine(Asn/Asn),Asn/serine(Ser),and Ser/Ser groups according to genotype at position 680.Logistic regression and correlation analyses were performed to identify the effect of these two polymorphisms on Gn consumption.Results:The frequency of Thr307Ala and Asn680Ser distribution was consistent with Hardy-Weinberg equilibrium(P>0.05).No significant difference was found in age,basal hormone levels for different genotype groups.Logistic regression analysis results revealed that patients with Ser680Ser genotype have a higher risk of requiring a high dose of Gn compared with patients with Asn680Asn genotype,while polymorphism of Thr307 Ala has no such effect.Conclusion:This study suggested that FSHR genotype Asn680Ser would be helpful in determining the dosage of Gn in COH;patients with Ser680Ser genotype may require higher dose of Gn.
文摘Health status of donor cows during superovulation is important to ensure optimal embryo quality at time of collection. Because nutritional and metabolic status impact embryo quality some form of nutritional supplementation is often provided before and during superovulation. OmniGen-AF® (OG) feeding has been shown to assist in the maintenance of animal health through regulation of metabolic status and balance and supporting aspects of immune function. We observed feeding donor cows OG decreased percent degenerate embryos recovered following superovulation increased serum progesterone concentration and improved in vitro embryo development. Evaluation of OG feeding on markers of metabolic function and inflammatory and immune function in beef cattle embryo donors are reported here. Similarly, cow metabolic and inflammatory response with repeated superovulation protocols is not known. Biomarkers to monitor and evaluate cow health during superovulation may provide management options to improve embryo recovery and quality. Twenty-four Angus cross-bred cattle were randomly assigned to four treatment groups, fed 0 or 56 g/hd/day for 49 days and superovulated with 200 or 400 mg Folltropin V (FSH). Blood was collected weekly for analyses. The protocol was repeated on all cows 90</span><span style="font-family:""> </span><span style="font-family:Verdana;">-</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">120 d later with cows reassigned to their original groups. No differences (</span><i><span style="font-family:Verdana;">P</span></i><span style="font-family:Verdana;"> > 0.10) were observed due to OG feeding or FSH dose on metabolic and inflammatory markers. Replicate exerted a significant effect where serum concentration of albumin, IL1β, IL6, PGE</span><sub><span style="font-family:Verdana;">2</span></sub><span style="font-family:Verdana;"> and leptin were lower (</span><i><span style="font-family:Verdana;">P</span></i><span style="font-family:Verdana;"> < 0.05) in Replicate 1 compared to 2. There was also a similar pattern of change in several of the metabolic and inflammatory markers during the superovulation protocol where concentrations were higher at the time of estrus and ovulation. Taken together, physiologic changes during the estrous cycle and the number of superovulation protocols can modulate metabolic markers and inflammatory response.
文摘Embryo quality is crucial when selecting embryos for transfer. Variation in quality may be attributed to poor oocytes, semen, stress, inflammation, and potential immune system dysregulation. OmniGen-AF<sup>®</sup> (OG) feeding supports immune system function and animal health. Our laboratory recently reported lower percent degenerate embryos recovered and increased plasma progesterone in beef cattle donors fed OG during superovulation. <i></span><i><span style="font-family:Verdana;">In vitro</span></i><span style="font-family:Verdana;"></i> development of embryos recovered from donor cows fed OG prior to collection is presented here. Embryos were recovered from 24 beef cows assigned to four treatment groups: 0 g OG/hd/d and 200 mg Folltropin<sup>®</sup>-V (FSH) (0/200);0 g OG/hd/d and 400 mg FSH (0/400), 56 g OG/hd/d, 200 mg FSH (56/200) and 56 g OG/hd/d and 400 mg FSH (56/400). Good to excellent quality early blastocysts were cultured for 8 d. and development through hatching, embryonic volume and plasminogen activator (PA) production were quantified. The complete protocol was repeated 90 - 120 d later as Replicate 2. Optimal development was observed by embryos recovered from 0/200 cows where percent blastocysts hatching was greater </span><span style="font-family:Verdana;">(</span><span style="font-family:Verdana;"><i></span><i><span style="font-family:Verdana;">P</span></i><span style="font-family:Verdana;"></i></span><span style="font-family:Verdana;"> < 0.05)</span> <span style="font-family:Verdana;">compared to 56/200 and 0/400 cows and embryonic volume was greatest (</span><span style="font-family:Verdana;"><i></span><i><span style="font-family:Verdana;">P</span></i><span style="font-family:Verdana;"></i></span><span style="font-family:Verdana;"> < 0.05) in Replicate 1. However, percent blastocysts hatching from 0/200 cows</span><span style="font-family:Verdana;"> was similar (<i></span><i><span style="font-family:Verdana;">P</span></i><span style="font-family:Verdana;"></i> > 0.10) to 56/400 cows and embryos recovered from 56/400 cows in Replicate 1 produced more (<i></span><i><span style="font-family:Verdana;">P</span></i><span style="font-family:Verdana;"></i> < 0.05) PA compared to all other groups. For cows superovulated with the standard 400-mg FSH dose, feeding OG supported </span><i><span style="font-family:Verdana;">in vitro</span></i><span style="font-family:Verdana;"> embryo development similar to that observed for 0/200 cows.
基金supported by the National Key Research&Developmental Program of China(2022YFC2703803,2018YFC1003700,2018YFC1003801,and 2023YFD1300501)the National Natural Science Foundation of China(32071132,31872792,32270904,32070839,32100913,82260291,and 32100686)+2 种基金China Postdoctoral Science Foundation(2021M700972)Institution of Higher Education Projects of Building First-class Discipline Construction in Ningxia Region(Biology)(NXYLXK2017B05)Doctoral Startup Foundation of Guizhou Medical University([2020]038)。
文摘In a growing follicle,the survival and maturation of the oocyte largely depend on support from somatic cells to facilitate FSH-induced mutual signaling and chemical communication.Although apoptosis and autophagy in somatic cells are involved in the process of FSH-induced follicular development,the underlying mechanisms require substantial study.According to our study,along with FSH-induced antral follicles(AFs)formation,both lysine-specific demethylase 1(LSD1)protein levels and autophagy increased simultaneously in granulosa cells(GCs)in a time-dependent manner,we therefore evaluated the importance of LSD upon facilitating the formation of AFs correlated to autophagy in GCs.Conditional knockout of Lsdl in GCs resulted in significantly decreased AF number and subfertility in females,accompanied by marked suppression of the autophagy in GCs.On the one hand,depletion of Lsd1 resulted in accumulation of Wilms tumor 1 homolog(WT1),at both the protein and mRNA levels.WT1 prevented the expression of FSH receptor(Fshr)in GCs and thus reduced the responsiveness of the secondary follicles to FSH induction.On the other hand,depletion of LSD1 resulted in suppressed level of autophagy by upregulation of ATG16L2 in GCs.We finally approved that LSD1 contributed to these sequential activities in GCs through its H3K4me2 demethylase activity.Therefore,the importance of LSD1 in GCs is attributable to its roles in both accelerating autophagy and suppressing WT1 expression to ensure the responsiveness of GCs to FSH during AFs formation.
基金supported by start-up funding from Shenzhen Institute of Advanced Technologythe National Natural Science Foundation of China(No.82271446).
文摘Alzheimer’s disease(AD)is the most common type of dementia.Almost two-thirds of patients with AD are female.The reason for the higher susceptibility to AD onset in women is unclear.However,hormone changes during the menopausal transition are known to be associated with AD.Most recently,we reported that follicle-stimulating hormone(FSH)promotes AD pathology and enhances cognitive dysfunctions via activating the CCAAT-enhancer-binding protein(C/EBPβ)/asparagine endopeptidase(AEP)pathway.This review summarizes our current understanding of the crucial role of the C/EBPβ/AEP pathway in driving AD pathogenesis by cleaving multiple critical AD players,including APP and Tau,explaining the roles and the mechanisms of FSH in increasing the susceptibility to AD in postmenopausal females.The FSH-C/EBPβ/AEP pathway may serve as a novel therapeutic target for the treatment of AD.
基金Supported by the Special Project for Scientific Research and Construction of a National Traditional Chinese Medicine Clinical Research Base of the China State Administration of Traditional Chinese Medicine(No.JD2X2012019)
文摘OBJECTIVE:To assess the efficacy of acupoint therapy combined with spine pinching in patients with menopausal syndrome.METHODS:This is a parallel,randomized,controlled,investigator-blinded trial.A total of 132 participants were randomly assigned to receive either acupoint therapy combined with spine pinching(intervention group)or tibolone therapy alone(control group).The intervention group received acupoint therapy combined with spine pinching three times per week for 4 weeks.The control group received 2.5 mg of tibolone once daily for 4 weeks.The primary outcome was the improved Kupperman score.The WHO quality of life scale was also used.The secondary aim was to identify those who would benefit from acupoint therapy combined with spine pinching based on the levels of follicle stimulating hormone(FSH)and luteinizing hormone(LH).RESULTS:In the intervention group,the improved Kupperman score was significantly decreased after treatment compared with before treatment.However,there were no differences between the intervention and control groups for any outcome.Changes in the physiology score presented negative outcomes in patients with a low FSH level with increasing body mass index(BMI)(P=0.0).In contrast,changes in the physiology score presented positive outcomes in patients with a moderate LH level with increasing BMI(P=0.0).The mean change in the physiology score of patients with a low FSH level and a BMI of≥25.7 kg/m2 was-7.17(range-10.94 to-3.40)after adjustments for age and disease duration.CONCLUSION:Acupoint therapy combined with spine pinching is effective in treating menopausal syndrome,especially in women with a moderate LH level.However,patients with a low FSH level had a negative outcome after acupoint therapy combined with spine pinching.In addition,patients with a BMI of>25.7 kg/m2 had a negative outcome after the intervention,regardless of hormone levels.
