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Allelic reprogramming of chromatin states in human early embryos

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National Science Review 2024年第3期11卷 58-71页

作者： Shenli Yuan Lei Gao Wenrong Tao Jianhong Zhan Gang Lu Jingye Zhang Chuanxin Zhang Lizhi Yi Zhenbo Liu Zhenzhen Hou Min Dai Han Zhao Zi-Jiang Chen Jiang Liu Keliang Wu center for reproductive medicine Shandong University CAS Key Laboratory of Genome Sciences and Information Collaborative Innovation Center of Genetics and Development Beijing Institute of Genomicsand China National Center for BioinformationChinese Academy of Sciences University of Chinese Academy of Sciences CUHK-SDU Joint Laboratory on reproductive Genetics School of Biomedical Sciences the Chinese University of Hong Kong Key Laboratory of reproductive Endocrinology of the Ministry of Education Shandong University center for reproductive medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University CAS center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

The reprogramming of parental epigenomes in human early embryos remains elusive. To what extent the characteristics of parental epigenomes are conserved between humans and mice is currently unknown. Here,we mapped parental haploid epigenomes using human parthenogenetic and androgenetic embryos. Human embryos have a larger portion of genome with parentally specific epigenetic states than mouse *** allelic patterns of epigenetic states for orthologous regions are not conserved between humans and mice. Nevertheless, it is conserved that maternal DNA methylation and paternal H3K27me3 are associated with the repression of two alleles in humans and mice. In addition, for DNA-methylation-dependent imprinting, we report 19 novel imprinted genes and their associated germline differentially methylated regions. Unlike in mice, H3K27me3-dependent imprinting is not observed in human early ***, allele-specific epigenomic reprogramming is different in humans and mice.

关键词： human embryo epigenetics reprogramming DNA methylation H3K27me3 chromatin accessibility

Novel PLCZ1 mutation caused polyspermy during in vitro fertilization

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Asian Journal of Andrology 2024年第4期26卷 389-395页

作者： Ke-Ya Tong Wei-Wei Liu Li-Wei Sun Dong-Yun Liu Ye-Zhou Xiang Chong Li Lu-Wei Chai Ke Chen Guo-Ning Huang Jing-Yu Li Chongqing Key Laboratory of Human Embryo Engineering Center for Reproductive MedicineWomen and Children’s Hospital of Chongqing Medical UniversityChongqing 400012China Chongqing Clinical Research center for reproductive medicine Center for Reproductive MedicineChongqing Health Center for Women and ChildrenChongqing 400012China.

Failure of oocyte activation,including polyspermy and defects in pronuclear(PN)formation,triggers early embryonic developmental *** studies have shown that phospholipase C zeta 1(PLCZ1)mutations cause failure of PN formation following intracytoplasmic sperm injection(ICSI);however,whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization(IVF)remains ***-exome sequencing(WES)was performed to identify candidate mutations in couples with primary *** sequencing was used to validate the *** PLCZ1-mutated sperm were injected into human and mouse oocytes to explore whether PN formation was *** oocyte activation(AOA)after ICSI was performed to overcome the failure of oocyte *** identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles,including a novel missense mutation c.1154C>T,*** formation failure was observed during the ICSI ***,injection of multiple PLCZ1-mutated sperm induced PN formation,suggesting that the Ca2+oscillations induced by the sperm exceeded the necessary threshold for PN *** after ICSI enabled normal fertilization,and all patients achieved successful *** findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking ***,this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.

关键词： AOA PLCZ1 polyspermy pronuclear formation

Effect of SARS-CoV-2 infection on semen parameters in sperm bank volunteers with normal sperm concentration

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Asian Journal of Andrology 2024年第3期26卷 328-332页

作者： Li Wang Wen-Kai Han Xiao-Hui Song Qi-Lin Zhang An-Quan Guan Yuan Gao Jin-Long Ma center for reproductive medicine Shandong UniversityJinan 250001China State Key Laboratory of reproductive medicine and Offspring Health ShandongUniversityJinan 250001China Key Laboratory of reproductive Endocrinology of Ministry of Education Shandong UniversityJinan 250001China Shandong KeyLaboratory of reproductive medicine Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250001China Shandong Provincial Clinical Research center for reproductive Health Jinan 250001China Shandong Technology Innovation center for reproductive Health Jinan 250001China NationalResearch center for Assisted reproductive Technology and reproductive Genetics Shandong UniversityJinan 250001China Research Unit of Gametogenesis andHealth of ART-Offspring Chinese Academy of Medical Sciences(No.2021RU001)Jinan 250001China

In this study,we aimed to assess the effect of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection on *** study comprised 110 sperm volunteers who self-reported SARS-CoV-2 infection from the Human Sperm Bank ofthe center for reproductive medicine,Shandong University(Jinan,China).The volunteers had normal sperm concentration *** volunteer provided semen samples before and after *** selected 90 days after infection as the cutoff *** parameters within 90 days after infection of 109 volunteers(group A)were compared with semen parameters before ***,semen parameters on or after 90 days after infection of 36 volunteers(group B)were compared with semen parameters ***,based on whether the volunteers had completed the three-dose SARS-CoV-2 vaccination booster,volunteersin group A and B were further divided into two subgroups *** parameters were compared before and after infection ineach *** results showed that in this cohort population,the semen quality in volunteers with normal sperm concentrationsbefore infection decreased after SARS-CoV-2 infection within 90 days,while the semen quality returned to preinfection levels after *** completion of a three-dose SARS-CoV-2 vaccination booster may exert a protective effect on semen quality after infection.

关键词： SARS-CoV-2 SARS-CoV-2 vaccination semen quality sperm donation sperm parameters

LSM14B coordinates protein component expression in the P-body and controls oocyte maturation

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Journal of Genetics and Genomics 2024年第1期51卷 48-60页

作者： Huiru Zhang Tao Zhang Xiang Wan Chang Chen Shu Wang Dongdong Qin Lufan Li Luping Yu Xin Wu State Key Laboratory of reproductive medicine and Offspring Health Nanjing Medical UniversityNanjingJiangsu 210029China center for reproductive medicine and Obstetrics and Gynecology Nanjing Drum Tower HospitalNanjing University Medical SchoolNanjingJiangsu 210029China

The generation of mature and healthy oocytes is the most critical event in the entire female reproductive process,and the mechanisms regulating this process remain to be ***,we demonstrate that Smith-like(LSM)family member 14B(LSM14B)regulates oocyte maturation,and the loss of LSM14B in mouse ovaries leads to abnormal oocyte MII arrest and female ***,we find the aberrant transcriptional activation,indicated by abnormal non-surrounded nucleolus and surrounded nucleolus oocyte proportions,and abnormal chromosome assembly and segregation in Lsm14b-deficient mouse *** global transcriptome analysis suggests that many transcripts involved in cytoplasmic processing body(P-body)function are altered in Lsm14b-deficient mouse *** of Lsm14b results in the expression and/or localization changes of P-body components(such as LSM14A,DCP1A,and 4E-T).Notably,DDX6,a key component of the P-body,is downregulated and accumulates in the nuclei in Lsm14b-deficient mouse *** together,our data suggest that LSM14B links mouse oocyte maturation to female fertility through the regulation of the P-body.

关键词： LSM14B P-body DDX6 MIl arrest Chromatin configuration

Cellular atlases of ovarian microenvironment alterations by diet and genetically-induced obesity

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Science China(Life Sciences) 2024年第1期67卷 51-66页

作者： Yonghui Jiang Xueying Gao Yue Liu Xueqi Yan Huangcong Shi Rusong Zhao Zi-Jiang Chen Fei Gao Han Zhao Shigang Zhao center for reproductive medicine Shandong UniversityJinan 250012China Research Unit of Gametogenesis and Health of ART-Offspring Chinese Academy of Medical Sciences(No.2021RU001)Jinan 250012China Key Laboratory of reproductive Endocrinology of Ministry of Education Shandong UniversityJinan 250012China Shandong Key Laboratory of reproductive medicine Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250012China Shandong Provincial Clinical Research center for reproductive Health Jinan 250012China National Research center of Assisted reproductive Technology and reproductive Genetics Shandong UniversityJinan 250012China The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhou 215000China center for reproductive medicine Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Shanghai Key Laboratory for Assisted Reproduction and reproductive Genetics Shanghai 200127China State Key Laboratory of Stem Cell and reproductive Biology Institute of ZoologyChinese Academy of ScienceBeijing 100101China

Obesity,which can arise from genetic or environmental factors,has been shown to cause serious damages to the reproductive *** 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 *** 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 ***,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 ***,HFD enhanced follicle-stimulating hormone(FSH)sensitivity and hormone conversion,while OB caused decreased sensitivity,inadequate steroid hormone conversion,and impaired follicular *** differences can be explained by the differential expression pattern of the transcription factor ***,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.

关键词： obesity ovarian microenvironment snRNA-seq Stereo-seq Foxo1

Impact of gonadotropin-releasing hormone agonist and hormone replacement therapy on pregnancy outcomes in single euploid frozen-thawed embryo transfer for patients with endometrial polyps

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生殖与发育医学(英文) 2024年第1期08卷 1-7页

作者： Zhao Qing Li Jie Wang Wei-Lin Liu Ying-Bo Li Jing Ni Tian-Xiang Zhou Wei Zhang Qian Yan Jun-Hao center for reproductive medicine Shandong University 3. Jinan 250012 4. China

Objective: Although consensus on the optimal endometrial preparation protocol for frozen-thawed embryo transfer (FET) is lacking, this is particularly true for patients with infertility and a history of endometrial polyps (EPs). In this study, we aimed to investigate whether a gonadotropin-releasing hormone agonist combined with hormone replacement therapy (GnRHa-HRT) could improve pregnancy outcomes in single euploid FET for patients with a history of ***: In this retrospective cohort study, 395 women who underwent their first single euploid FET cycle were divided into groups according to endometrial preparation protocols as follows: natural cycle (NC) (n = 220), hormone replacement therapy (HRT) (n = 122), and GnRHa-HRT groups (n = 53). Subsequently, the FET cycles in the three groups were subdivided according to maternal age. All patients underwent hysteroscopic polypectomy before FET, and their EPs were confirmed by ***: No statistically significant differences were observed in live birth rates among the three groups (58.64%vs. 58.20%vs. 56.60%,P = 0.964). Furthermore, the rates of miscarriage, ectopic pregnancy, premature live birth, and pregnancy complications were comparable among the three groups (P >0.05). After adjusting for potential confounding factors, no significant differences in pregnancy outcomes were reported between the groups (adjusted odds ratios [OR] and 95% credible intervals [CI] for live birth rate, HRTvs. NC: 1.119, 0.660–1.896,P = 0.677; GnRHa-HRTvs. NC: 1.165, 0.610–2.226,P = 0.643). Additionally, the pregnancy outcomes of the FET cycle were not influenced by the endometrial preparation protocols in the subgroups when stratified by maternal age (P >0.05).Conclusion: GnRHa-HRT did not improve the pregnancy outcomes of the single euploid FET in patients with a history of EPs.

关键词： Endometrial polyps Frozen-thawed embryo transfer GnRHa Hormone replacement therapy Preimplantation genetic testing

Adenylate kinase phosphate energy shuttle underlies energetic communication in flagellar axonemes

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Science China(Life Sciences) 2024年第8期67卷 1697-1714页

作者： Huan Wu Yanman Zhang Yuqian Li Shuya Sun Jintao Zhang Qingsong Xie Yue Dong Shushu Zhou Xuan Sha Kuokuo Li Jinyi Chen Xin Zhang Yang Gao Qunshan Shen Guanxiong Wang Xiaomin Zha Zongliu Duan Dongdong Tang Chuan Xu Hao Geng Mingrong Lv Yuping Xu Ping Zhou Zhaolian Wei Rong Hua Yunxia Cao Mingxi Liu Xiaojin He reproductive medicine center Department of Obstetrics and GynecologyThe First Affiliated Hospital of Anhui Medical UniversityHefei 230022China State Key Laboratory of reproductive medicine and Offspring Health Department of Histology and EmbryologySchool of Basic Medical SciencesNanjing Medical UniversityNanjing 210029China State Key Laboratory of reproductive medicine and Offspring Health The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityTaizhou School of Clinical MedicineNanjing Medical UniversityNanjing 211166China reproductive medicine center Department of Obstetrics and GynecologyShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China State Key Laboratory of reproductive medicine and Offspring Health Clinical Center of Reproductive MedicineThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China NHC Key Laboratory of Study on Abnormal Gametes and reproductive Tract(Anhui Medical University) Hefei 230032China Key Laboratory of Population Health Across Life Cycle(Anhui Medical University) Ministry of Education of the People’s Republic of ChinaHefei 230032China Anhui Province Key Laboratory of reproductive Health and Genetics Hefei 230032China Biopreservation and Artificial Organs Anhui Provincial Engineering Research CenterAnhui Medical UniversityHefei 230032China

The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across *** shuttles,particularly adenylate kinase(AK)and creatine kinase(CK),are pivotal in the efficient transfer of intracellular ATP,showing distinct tissue-and ***,the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups,of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across *** AK8 and AK9 were found to be indispensable to male reproduction after analysis of an infertile male *** mouse models showed that AK8 and AK9 were central to promoting sperm *** combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke(RS)of the *** of various human and mouse sperm samples with substructural damage,including the presence of multiple RS subunits,showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar *** an ATP probe together with metabolomic analysis,it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme,and were concentrated at sites associated with energy consumption in the *** findings indicate a novel function for RS beyond its structural role,namely,the regulation of ATP *** conclusion,the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella.

关键词： adenylate kinase Subgroup III AKs AK8 AK9 male infertility ATP transfer radial spoke

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DENND1A desensitizes granulosa cells to FSH by arresting intracellular FSHR transportation

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Science China(Life Sciences) 2024年第8期67卷 1620-1634页

作者： Yunde Dou Rusong Zhao Han Wu Zhiheng Yu Changjian Yin Jie Yang Chaoyan Yang Xiaohua Luan Yixiao Cheng Tao Huang Yuehong Bian Shan Han Yuqing Zhang Xin Xu Zi-Jiang Chen Han Zhao Shigang Zhao Institute of Women Children and Reproductive HealthShandong UniversityJinan 250012China State Key Laboratory of reproductive medicine and Offspring Health Jinan 250012China Key laboratory of reproductive Endocrinology of Ministry of Education Shandong UniversityJinan 250012China Shandong Key Laboratory of reproductive medicine Shandong UniversityJinan 250012China Shandong Provincial Clinical Research center for reproductive Health Jinan 250012China National Research center for Assisted reproductive Technology and reproductive Genetics Shandong UniversityJinan 250012China The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal HospitalNanjing Medical UniversitySuzhou 215008China Gusu School Nanjing Medical UniversitySuzhou 215000China Guangdong Provincial People’s Hospital Guangdong Academy of Medical SciencesGuangzhou 510080China Guangdong-Hong Kong Metabolism&Reproduction Joint Laboratory Guangdong Second Provincial General HospitalGuangzhou 510317China reproductive medicine center Guangdong Second Provincial General HospitalGuangzhou 510317China Research Unit of Gametogenesis and Health of ART-Offspring Chinese Academy of Medical Sciences(No.2021RU001)Jinan 250012China Shanghai Key Laboratory for Assisted Reproduction and reproductive Genetics Shanghai 200127China center for reproductive medicine Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China

Polycystic ovary syndrome(PCOS)is a complex ***-wide association studies(GWAS)have identified several genes associated with this condition,including ***1A encodes a clathrin-binding protein that functions as a guanine nucleotide exchange factor involved in vesicular ***,the specific role of DENND1A in reproductive hormone abnormalities and follicle development disorders in PCOS remain poorly *** this study,we investigated DENND1A expression in ovarian granulosa cells(GCs)from PCOS patients and its correlation with *** results revealed an upregulation of DENND1A expression in GCs from PCOS cases,which was positively correlated with testosterone *** further explore the functional implications of DENND1A,we generated a transgenic mouse model overexpressing Dennd1a(TG mice).These TG mice exhibited subfertility,irregular estrous cycles,and increased testosterone production following PMSG ***,the TG mice displayed diminished responsiveness to FSH,characterized by smaller ovary size,less well-developed follicles,and abnormal expressions of FSH-priming ***,we found that Dennd1a overexpression disrupted the intracellular trafficking of follicle stimulating hormone receptor(FSHR),promoting its internalization and inhibiting *** findings shed light on the reproductive role of DENND1A and uncover the underlying mechanisms,thereby contributing valuable insights into the pathogenesis of PCOS and providing potential avenues for drug design in PCOS treatment.

关键词： PCOS DENND1A FSHR ovarian granulosa cells

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Exploring the impact of pericentric inversion of chromosome 9 on fertility in sperm donors

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Asian Journal of Andrology 2024年第3期26卷 302-307页

作者： Qian Liu Wen-Jun Zhou Zeng-Hui Huang Xiu-Hai Huang Jian Wu Xi-Ren Ji Xue-Feng Luo Yu-Ling Tang Rui-Jun Wang Li-Qing Fan Chuan Huang Wen-Bing Zhu Institute of reproductive and Stem Cell Engineering Basic Medicine CollegeCentral South UniversityChangsha 410013China Clinical Research center for Reproduction and Genetics in Hunan Province Reproductive and Genetic Hospital of CITIC-XiangyaChangsha 410005China

Pericentric inversion of chromosome 9(inv[9])is a common chromosomal structural variant,but its impact on clinical outcomesremains *** screening criteria of sperm banks are rarely mentioned to individuals with inv(9).In this study,we evaluatedthe fertility of sperm donors with inv(9)who met eligibility criteria for sperm banks(inv[9]-eligible donors).From March 2004 toMay 2022,chromosomal analysis of 16124 sperm donors at CITIC-Xiangya Human Sperm Bank in Hunan Province(Changsha,China)found that 251(1.6%)had chromosome variations,with inv(9)being the most prevalent at 1.1%.All 169 inv(9)-eligibledonors were contacted to collect fertility outcome data,along with 206 eligible donors without inv(9)as *** addition,semen samples from inv(9)-eligible donors and eligible donors underwent assessments of sperm fluorescence in situ hybridization(FISH),mitochondrial membrane potential,DNA fragmentation index,acrosome integrity,reactive oxygen species(ROS),andsperm *** showed that inv(9)did not significantly increase reproductive risks *** detecting ROSlevel differences,the clinical impact may be *** study provides new data on the inv(9)population that can serveas a valuable reference for decision-making by sperm banks as well as for genetic counseling and clinical guidance for individualscarrying inv(9)variant.

关键词： male fertility pericentric inversion of chromosome 9 sperm bank sperm functional parameters