Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40.It represents a significant detriment to female fertility.However,the known POI...Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40.It represents a significant detriment to female fertility.However,the known POI-causative genes currently account for only a fraction of cases.To elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in RNF111.In a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 variants.These variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 variants.Notably,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling pathway.Our analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and humans.To further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian reserve.Additionally,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse ovaries.In conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.展开更多
Obesity impacts human health in more than one way.The influence of obesity on human reproduction and fertility has been extensively examined.Bariatric surgery(BS)has been used as an effective tool to achieve long-term...Obesity impacts human health in more than one way.The influence of obesity on human reproduction and fertility has been extensively examined.Bariatric surgery(BS)has been used as an effective tool to achieve long-term weight loss in both sexes.BS improves hormonal profiling,increasing the odds of spontaneous pregnancy and success rates following assisted reproductive techniques in infertile females.For obese males,BS does improve sexual function and hormonal profile;however,conflicting reports discuss reduced sperm parameters following BS.Although the benefits of BS in the fertility field are acknowledged,many areas call for further research,like choosing the safest surgical techniques,determining the optimal timing to get pregnant,and resolving the uncertainty of sperm parameters.展开更多
Objective This study examined humanin expression in rat ovarian tissue,its cellular localization,and its correlation with rat age under physiological conditions.Methods A total of 40 Sprague-Dawley rats of various age...Objective This study examined humanin expression in rat ovarian tissue,its cellular localization,and its correlation with rat age under physiological conditions.Methods A total of 40 Sprague-Dawley rats of various ages(2,12,30,and 60 days old and 1 year old)were grouped by age.Immunofluorescence and immunohistochemical techniques were used to observe humanin expression and cellular location in the ovarian tissues of rats from each age group.In addition,Western blotting and Real-time quantitative reverse transcription PCR(qRT-PCR)techniques were used to measure humanin expression level in the ovarian tissues of rats from each age group.Results The immunofluorescence and immunohistochemical results confirmed that humanin was expressed in rat ovarian tissues.In addition,cellular localization analysis showed that humanin was expressed in the cytoplasm of oocytes,interstitial cells,granulosa cells and theca cells in all levels of follicles after the primary follicles,and in the corpus luteum.The qRT-PCR results revealed that the level of humanin expression in the ovarian tissues of 12-day-old rats was non-significantly higher than that in the ovarian tissues of 2-day-old rats(P>0.05),whereas the levels of humanin expression in the ovarian tissues of 30-day-old,60-day-old,and 1-year-old rats were significantly lower than that in the ovarian tissues of 2-day-old rats(P<0.05).The Western blotting results demonstrated that the levels of humanin protein expression in the ovarian tissues of 60-day-old and 1-year-old rats were significantly lower than those of 2-day-old rats(P<0.01),whereas there was no significant difference in the level of humanin protein expression between the ovarian tissues of 12-day-old and 30-day-old rats.Conclusion This study confirmed that humanin is expressed in the cytoplasm of various cells in rat ovarian tissues.Moreover,the level of humanin expression was highest in the ovarian tissues of 12-day-old rats,and it subsequently decreased with age.The changes in the expression of humanin in the ovary of rats at different ages will lay the foundation for the role of humanin in ovarian aging.The effect of humanin on ovarian function is worthy of further study in the future.展开更多
The effects of delayed mating on the copulation duration, female fertility, fecundity, egg fertility, longevity and the number days alive after mating of females of diamondback moth （DBM）, Plutella xylostella, were ...The effects of delayed mating on the copulation duration, female fertility, fecundity, egg fertility, longevity and the number days alive after mating of females of diamondback moth （DBM）, Plutella xylostella, were studied. When male mating was delayed, the female fertility, fecundity, egg fertility, longevity and number days alive after mating of DBM decreased, and there was a negative correlation between the age of the moth with those variables except copulation duration. When female mating was delayed, the female fertility, fecundity, percent egg fertility and number days alive after mating of DBM also decreased, but the longevity increased, which also showed a negative relationship between the age of the moth with the variables except copulation duration and longevity. When both males and females delayed mating, the female fertility and fecundity decreased; egg fertility was affected marginally, and the longevity of females increased. The moth age was negatively correlated with those variables.展开更多
Mitochondria are important in eukaryotic cells due to their functions in energy production and regulation over other cellular activities.Oocytes are produced by a long and precisely controlled process,the dysfunction ...Mitochondria are important in eukaryotic cells due to their functions in energy production and regulation over other cellular activities.Oocytes are produced by a long and precisely controlled process,the dysfunction of which leads to impaired female fertility.As oocytes mature,mitochondria are constantly under the regulation of nuclear genes,the process of which can be modulated by extracellular signals.Understanding how nuclear genes regulate mitochondrial functions is important for studying animal reproduction and human fertility.As more and more genes regulating mitochondrial functions in oocytes are being revealed,new approaches for improving female fertility in both human and animals through mitochondria can be developed.展开更多
A man having severe oligospermia, due to partial maturation arrest at spermatid stage, was given low dose estrogen-testosterone combination therapy for three months. His sperm count increased enormously, following whi...A man having severe oligospermia, due to partial maturation arrest at spermatid stage, was given low dose estrogen-testosterone combination therapy for three months. His sperm count increased enormously, following which his wife conceived and delivered a healthy baby at term.展开更多
基金supported by the National Natural Science Foundation of China(32288101)the National Key Research and Development Program of China(2021YFC2701400)Shenkang Clinical Technology Innovation Project(SHDC22021219)。
文摘Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40.It represents a significant detriment to female fertility.However,the known POI-causative genes currently account for only a fraction of cases.To elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in RNF111.In a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 variants.These variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 variants.Notably,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling pathway.Our analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and humans.To further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian reserve.Additionally,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse ovaries.In conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.
文摘Obesity impacts human health in more than one way.The influence of obesity on human reproduction and fertility has been extensively examined.Bariatric surgery(BS)has been used as an effective tool to achieve long-term weight loss in both sexes.BS improves hormonal profiling,increasing the odds of spontaneous pregnancy and success rates following assisted reproductive techniques in infertile females.For obese males,BS does improve sexual function and hormonal profile;however,conflicting reports discuss reduced sperm parameters following BS.Although the benefits of BS in the fertility field are acknowledged,many areas call for further research,like choosing the safest surgical techniques,determining the optimal timing to get pregnant,and resolving the uncertainty of sperm parameters.
文摘Objective This study examined humanin expression in rat ovarian tissue,its cellular localization,and its correlation with rat age under physiological conditions.Methods A total of 40 Sprague-Dawley rats of various ages(2,12,30,and 60 days old and 1 year old)were grouped by age.Immunofluorescence and immunohistochemical techniques were used to observe humanin expression and cellular location in the ovarian tissues of rats from each age group.In addition,Western blotting and Real-time quantitative reverse transcription PCR(qRT-PCR)techniques were used to measure humanin expression level in the ovarian tissues of rats from each age group.Results The immunofluorescence and immunohistochemical results confirmed that humanin was expressed in rat ovarian tissues.In addition,cellular localization analysis showed that humanin was expressed in the cytoplasm of oocytes,interstitial cells,granulosa cells and theca cells in all levels of follicles after the primary follicles,and in the corpus luteum.The qRT-PCR results revealed that the level of humanin expression in the ovarian tissues of 12-day-old rats was non-significantly higher than that in the ovarian tissues of 2-day-old rats(P>0.05),whereas the levels of humanin expression in the ovarian tissues of 30-day-old,60-day-old,and 1-year-old rats were significantly lower than that in the ovarian tissues of 2-day-old rats(P<0.05).The Western blotting results demonstrated that the levels of humanin protein expression in the ovarian tissues of 60-day-old and 1-year-old rats were significantly lower than those of 2-day-old rats(P<0.01),whereas there was no significant difference in the level of humanin protein expression between the ovarian tissues of 12-day-old and 30-day-old rats.Conclusion This study confirmed that humanin is expressed in the cytoplasm of various cells in rat ovarian tissues.Moreover,the level of humanin expression was highest in the ovarian tissues of 12-day-old rats,and it subsequently decreased with age.The changes in the expression of humanin in the ovary of rats at different ages will lay the foundation for the role of humanin in ovarian aging.The effect of humanin on ovarian function is worthy of further study in the future.
文摘The effects of delayed mating on the copulation duration, female fertility, fecundity, egg fertility, longevity and the number days alive after mating of females of diamondback moth （DBM）, Plutella xylostella, were studied. When male mating was delayed, the female fertility, fecundity, egg fertility, longevity and number days alive after mating of DBM decreased, and there was a negative correlation between the age of the moth with those variables except copulation duration. When female mating was delayed, the female fertility, fecundity, percent egg fertility and number days alive after mating of DBM also decreased, but the longevity increased, which also showed a negative relationship between the age of the moth with the variables except copulation duration and longevity. When both males and females delayed mating, the female fertility and fecundity decreased; egg fertility was affected marginally, and the longevity of females increased. The moth age was negatively correlated with those variables.
基金the National Natural Science Foundation of China(Nos.41776144 and 32072954)Zhejiang Province Public Welfare Technology Application Research Project(including Natural Science Foundation)(No.LGF20C120001).
文摘Mitochondria are important in eukaryotic cells due to their functions in energy production and regulation over other cellular activities.Oocytes are produced by a long and precisely controlled process,the dysfunction of which leads to impaired female fertility.As oocytes mature,mitochondria are constantly under the regulation of nuclear genes,the process of which can be modulated by extracellular signals.Understanding how nuclear genes regulate mitochondrial functions is important for studying animal reproduction and human fertility.As more and more genes regulating mitochondrial functions in oocytes are being revealed,new approaches for improving female fertility in both human and animals through mitochondria can be developed.
文摘A man having severe oligospermia, due to partial maturation arrest at spermatid stage, was given low dose estrogen-testosterone combination therapy for three months. His sperm count increased enormously, following which his wife conceived and delivered a healthy baby at term.
