Meiosis is a specialized cell division for producing haploid gametes in sexually reproducing organisms.In this study,we have independently identified a novel meiosis protein male meiosis recombination regulator(MAMERR...Meiosis is a specialized cell division for producing haploid gametes in sexually reproducing organisms.In this study,we have independently identified a novel meiosis protein male meiosis recombination regulator(MAMERR)/4930432 K21 Rik and showed that it is indispensable for meiosis prophase I progression in male mice.Using super-resolution structured illumination microscopy,we found that MAMERR functions at the same double-strand breaks as the replication protein A and meiosis-specific with OB domains/spermatogenesis associated 22 complex.We generated a Mamerr-deficient mouse model by deleting exons 3 e6 and found that most of Mamerrà/àspermatocytes were arrested at pachynema and failed to progress to diplonema,although they exhibited almost intact synapsis and progression to the pachytene stage along with XY body formation.Further mechanistic studies revealed that the recruitment of DMC1/RAD51 and heat shock factor 2 ebinding protein in Mamerrà/àspermatocytes was only mildly impaired with a partial reduction in double-strand break repair,whereas a substantial reduction in ubiquitination on the autosomal axes and on the XY body appeared as a major phenotype in Mamerrà/àspermatocytes.We propose that MAMERR may participate in meiotic prophase I progression by regulating the ubiquitination of key meiotic proteins on autosomes and XY chromosomes,and in the absence of MAMERR,the repressed ubiquitination of key meiotic proteins leads to pachytene arrest and cell death.展开更多
Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection has swept the globe for 3 years(Zhou et al.,2020).With the nationwide relaxation of controls on the coronavirus disease 2019(COVID-19)ep...Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection has swept the globe for 3 years(Zhou et al.,2020).With the nationwide relaxation of controls on the coronavirus disease 2019(COVID-19)epidemic since December 2022 in China,fertility and in vitro fertilization(IVF)centers are receiving increasing numbers of infected patients.展开更多
Few large-scale studies have systematically examined the effects of maternal exposure to fine particulate matter(PM_(2.5))on live birth in women undergoing in vitro fertilization(IVF).This study aimed to investigate t...Few large-scale studies have systematically examined the effects of maternal exposure to fine particulate matter(PM_(2.5))on live birth in women undergoing in vitro fertilization(IVF).This study aimed to investigate the associations between ambient PM_(2.5)exposure and live birth in women treated with IVF,and determine critical periods,key failure events,and vulnerable populations affected by such exposure.We included 58,637 patients from six reproductive centers in China between 2016 and 2021.We defined six exposure windows and adopted logistic regression with random-effect models to investigate the associations between PM_(2.5)exposure and live birth.We further categorized live birth failure as implantation failure,biochemical pregnancy loss,and miscarriage,to determine at which stage PM_(2.5)exposure caused the live birth failure.Subgroup analyses were conducted by female age,ovarian response,embryo quality,and transplantation protocol.For each 10μg/m^(3)increase in PM_(2.5)concentration during follicle growth phase,preantral-antral follicle phase,and antral-mature follicle phase,the odds ratios for live birth were 0.966[95%confidence interval(CI):0.938,0.995],0.967(0.939,0.996),and 0.978(0.958,0.998),respectively.PM_(2.5)during these stages was significantly associated only with an increased likelihood of implantation failure,highlighting adverse impact of ambient PM_(2.5)on early pregnancy outcome.In addition,we observed relatively stronger associations in women with poor ovarian response,compromised embryo quality,and those undergoing fresh or double embryo transfers.This large-scale population-based study demonstrated the detrimental effects of high PM_(2.5)exposure for IVF women,shedding light on clinical and public health practices.展开更多
Obesity,which can arise from genetic or environmental factors,has been shown to cause serious damages to the reproductive system.The ovary,as one of the primary regulators of female fertility,is a complex organ compri...Obesity,which can arise from genetic or environmental factors,has been shown to cause serious damages to the reproductive system.The ovary,as one of the primary regulators of female fertility,is a complex organ comprised of heterogeneous cell types that work together to maintain a normal ovarian microenvironment(OME).Despite its importance,the effect of obesity on the entire ovary remains poorly documented.In this study,we performed ovary single-cell and nanoscale spatial RNA sequencing to investigate how the OME changed under different kinds of obesity,including high-fat diet(HFD)induced obesity and Leptin ablation induced obesity(OB).Our results demonstrate that OB,but not HFD,dramatically altered the proportion of ovarian granulosa cells,theca-interstitial cells,luteal cells,and endothelial cells.Furthermore,based on the spatial dynamics of follicular development,we defined four subpopulations of granulosa cell and found that obesity drastically disrupted the differentiation of mural granulosa cells from small to large antral follicles.Functionally,HFD enhanced follicle-stimulating hormone(FSH)sensitivity and hormone conversion,while OB caused decreased sensitivity,inadequate steroid hormone conversion,and impaired follicular development.These differences can be explained by the differential expression pattern of the transcription factor Foxo1.Overall,our study provides a powerful and high-resolution resource for profiling obesity-induced OME and offers insights into the diverse effects of obesity on female reproductive disorders.展开更多
Dear Editor,Previously,the Mendelian phe no types in huma n oocyte maturation arrest,fertilization failure and early embryonic arrest,are largely underestimated.In recent years,"missing"Men delian phe no typ...Dear Editor,Previously,the Mendelian phe no types in huma n oocyte maturation arrest,fertilization failure and early embryonic arrest,are largely underestimated.In recent years,"missing"Men delian phe no types and genes in these processes are beginning to be uncovered by us and others(Huang et al.,2014;Alazami et al..2015;Feng et al.,2016;Xu et al.,2016;Chen et al.,2017;Sang et al.,2019).However,the genetic basis for majority of patients resulting from abnormalities in these phe no types remains to be elucidated.展开更多
基金supported by grants from the Hong Kong Research Grant Council(17114920,K.L.and R.H.W.L.)the University of Hong Kong(K.L.)+3 种基金the Sanming Project of Medicine in Shenzhen,China(SZSM201612083,W.S.B.Y.)High Level-Hospital Program,Health Commission of Guangdong Province,China(HKUSZH201902018,K.L.)Shenzhen-Hong Kong Innovation Circle Type D(K.L.)a grant from the NIH/NIGMS(National Institute of General Medical Sciences)R35GM118052(P.J.W.)
文摘Meiosis is a specialized cell division for producing haploid gametes in sexually reproducing organisms.In this study,we have independently identified a novel meiosis protein male meiosis recombination regulator(MAMERR)/4930432 K21 Rik and showed that it is indispensable for meiosis prophase I progression in male mice.Using super-resolution structured illumination microscopy,we found that MAMERR functions at the same double-strand breaks as the replication protein A and meiosis-specific with OB domains/spermatogenesis associated 22 complex.We generated a Mamerr-deficient mouse model by deleting exons 3 e6 and found that most of Mamerrà/àspermatocytes were arrested at pachynema and failed to progress to diplonema,although they exhibited almost intact synapsis and progression to the pachytene stage along with XY body formation.Further mechanistic studies revealed that the recruitment of DMC1/RAD51 and heat shock factor 2 ebinding protein in Mamerrà/àspermatocytes was only mildly impaired with a partial reduction in double-strand break repair,whereas a substantial reduction in ubiquitination on the autosomal axes and on the XY body appeared as a major phenotype in Mamerrà/àspermatocytes.We propose that MAMERR may participate in meiotic prophase I progression by regulating the ubiquitination of key meiotic proteins on autosomes and XY chromosomes,and in the absence of MAMERR,the repressed ubiquitination of key meiotic proteins leads to pachytene arrest and cell death.
基金supported by the National Natural Science Foundation of China(31988101,82192874,82130046)the National Key Research and Development Program of China(2021YFC2700400)+3 种基金CAMS Innovation Fund for Medical Sciences(2021-I2M-5-001)Shandong Provincial Key Research and Development Program(2020ZLYS02)Taishan Scholars Program of Shandong Province(ts20190988,tsqn201909194)Innovative research team of high-level local universities in Shanghai(SHSMU-ZLCX20210200,SHSMUZLCX20210201)。
文摘Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection has swept the globe for 3 years(Zhou et al.,2020).With the nationwide relaxation of controls on the coronavirus disease 2019(COVID-19)epidemic since December 2022 in China,fertility and in vitro fertilization(IVF)centers are receiving increasing numbers of infected patients.
基金supported by Science and Technology Commission of Shanghai Municipality(23Y11909600)Clinical Research Plan of Shanghai Hospital Development Center(SHDC2020CR4080)National Natural Science Foundation of China(81871213,81671468).
文摘Few large-scale studies have systematically examined the effects of maternal exposure to fine particulate matter(PM_(2.5))on live birth in women undergoing in vitro fertilization(IVF).This study aimed to investigate the associations between ambient PM_(2.5)exposure and live birth in women treated with IVF,and determine critical periods,key failure events,and vulnerable populations affected by such exposure.We included 58,637 patients from six reproductive centers in China between 2016 and 2021.We defined six exposure windows and adopted logistic regression with random-effect models to investigate the associations between PM_(2.5)exposure and live birth.We further categorized live birth failure as implantation failure,biochemical pregnancy loss,and miscarriage,to determine at which stage PM_(2.5)exposure caused the live birth failure.Subgroup analyses were conducted by female age,ovarian response,embryo quality,and transplantation protocol.For each 10μg/m^(3)increase in PM_(2.5)concentration during follicle growth phase,preantral-antral follicle phase,and antral-mature follicle phase,the odds ratios for live birth were 0.966[95%confidence interval(CI):0.938,0.995],0.967(0.939,0.996),and 0.978(0.958,0.998),respectively.PM_(2.5)during these stages was significantly associated only with an increased likelihood of implantation failure,highlighting adverse impact of ambient PM_(2.5)on early pregnancy outcome.In addition,we observed relatively stronger associations in women with poor ovarian response,compromised embryo quality,and those undergoing fresh or double embryo transfers.This large-scale population-based study demonstrated the detrimental effects of high PM_(2.5)exposure for IVF women,shedding light on clinical and public health practices.
基金This work was supported by the National Key Research and Development Program of China(2021YFC2700400,2018YFC1004303)the National Natural Science Foundation of China(31988101,82201798,82192874,82071606,82101707)+3 种基金CAMS Innovation Fund for Medical Sciences(2021-I2M-5-001)Shandong Provincial Key Research and Development Program(2020ZLYS02)the Taishan Scholars Program of Shandong Province(ts20190988)the Fundamental Research Funds of Shandong University.
文摘Obesity,which can arise from genetic or environmental factors,has been shown to cause serious damages to the reproductive system.The ovary,as one of the primary regulators of female fertility,is a complex organ comprised of heterogeneous cell types that work together to maintain a normal ovarian microenvironment(OME).Despite its importance,the effect of obesity on the entire ovary remains poorly documented.In this study,we performed ovary single-cell and nanoscale spatial RNA sequencing to investigate how the OME changed under different kinds of obesity,including high-fat diet(HFD)induced obesity and Leptin ablation induced obesity(OB).Our results demonstrate that OB,but not HFD,dramatically altered the proportion of ovarian granulosa cells,theca-interstitial cells,luteal cells,and endothelial cells.Furthermore,based on the spatial dynamics of follicular development,we defined four subpopulations of granulosa cell and found that obesity drastically disrupted the differentiation of mural granulosa cells from small to large antral follicles.Functionally,HFD enhanced follicle-stimulating hormone(FSH)sensitivity and hormone conversion,while OB caused decreased sensitivity,inadequate steroid hormone conversion,and impaired follicular development.These differences can be explained by the differential expression pattern of the transcription factor Foxo1.Overall,our study provides a powerful and high-resolution resource for profiling obesity-induced OME and offers insights into the diverse effects of obesity on female reproductive disorders.
文摘Dear Editor,Previously,the Mendelian phe no types in huma n oocyte maturation arrest,fertilization failure and early embryonic arrest,are largely underestimated.In recent years,"missing"Men delian phe no types and genes in these processes are beginning to be uncovered by us and others(Huang et al.,2014;Alazami et al..2015;Feng et al.,2016;Xu et al.,2016;Chen et al.,2017;Sang et al.,2019).However,the genetic basis for majority of patients resulting from abnormalities in these phe no types remains to be elucidated.
