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Allelic reprogramming of chromatin states in human early embryos

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

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ZP2:the precision regulator of egg coat architecture during fertilization

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Science China(Life sciences) 2024年第8期67卷 1779-1780页

作者： Yi Dong Shigang Zhao Han Zhao State Key Laboratory of reproductive Medicine and Offspring Health Center for Reproductive MedicineInstitute of WomenChildren and Reproductive HealthShandong UniversityJinan 250012China

In a recent study published in Cell,(Nishio et al.,2024)elucidated the molecular regulatory mechanism through which organisms prevent *** process intricately involves conformational changes in the zona pellucida(ZP)*** authors present a fascinating mechanism whereby post-fertilization cleavage of the ZP subunit ZP2 triggers its oligomerization,leading to crosslinking of filaments to harden the egg coat and prevent *** also systematically analyzed the pattern of ZP filament assembly,which revealed that two protofilaments comprising type I(ZP3)and type II(ZP1/ZP2/ZP4)components interlock to form a left-handed double helix *** findings are immensely beneficial for understanding the specific role of the egg coat,providing a plethora of insights.

关键词： mechanism finding crosslinking

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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

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Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics

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Protein & Cell 2024年第5期15卷 364-384页

作者： Huifen Lu Ying Jing Chen Zhang Shuai Ma Weiqi Zhang Daoyuan Huang Bin Zhang Yuesheng Zuo Yingying Qin Guang-Hui Liu Yang Yu Jing Qu Si Wang Advanced Innovation center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of sciences Beijing 100049China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Institute for Stem cell and Regeneration CASBeijing 100101China China National center for Bioinformation Beijing 100101China The Fifth People’s Hospital of Chongqing Chongqing 400062China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish center for Education and Research Beijing 101408China Department of Obstetrics and Gynecology Center for Reproductive MedicinePeking UniversityThird HospitalBeijing 100191China Clinical Stem Cell Research center Peking UniversityThird HospitalBeijing 100191China center for reproductive Medicine Cheeloo College of MedicineShandong UniversityJinan 250012China Key Laboratory of reproductive Endocrinology of Ministry of Education National Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthJinan 250012China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Biomarker Consortium Beijing 100101China

The ovary is indispensable for female reproduction,and its age-dependent functional decline is the primary cause of ***,the molecular basis of ovarian aging in higher vertebrates remains poorly ***,we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular determinants in young primate ovaries and compare these to aged primate *** a global view,somatic cells within the non-follicle region undergo more pronounced transcriptional fluctuation relative to those in the follicle region,likely constituting a hostile microenvironment that facilitates ovarian ***,we uncovered that inflammation,the senescent-associated secretory phenotype,senescence,and fibrosis are the likely primary contributors to ovarian aging(PCOA).Of note,we identified spatial co-localization between a PCOA-featured spot and an unappreciated MT2(Metallothionein 2)highly expressing spot(MT2^(high))characterized by high levels of inflammation,potentially serving as an aging hotspot in the primate ***,with advanced age,a subpopulation of MT2^(high)accumulates,likely disseminating and amplifying the senescent signal *** study establishes the first primate spatiotemporal transcriptomic atlas,advancing our understanding of mechanistic determinants underpinning primate ovarian aging and unraveling potential biomarkers and therapeutic targets for aging and age-associated human ovarian disorders.

关键词： spatial transcriptome primate ovary aging senescence inflammation

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Nurses'critical thinking disposition and professional commitment:a cross-sectional study

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Frontiers of Nursing 2024年第1期11卷 119-126页

作者： Mahtab Allah Tavakoli Golnaz Foroughameri Jamileh Farokhzadian Sedigheh Khodabandeh Shahraki Nursing Research center Kerman University of Medical SciencesKerman ***Iran reproductive Health Family and Population Research CenterKerman University of Medical SciencesKerman ***Iran

Objective:High-quality and successful nursing care delivery in a variety of situations requires critical thinking training and professional *** present study aimed to investigate critical thinking disposition,professional commitment,and the relationship between these 2 variables among ***:As a result of stratified random sampling,201 nurses were enrolled in the present cross-sectional *** were gathered using a socio-demographic form,the Critical Thinking Disposition Inventory(CTDI),and the Nurses'Professional Commitment Scale(NPCS).Results:Although the critical thinking disposition scores were at a moderate level(115.70±13.55),the mean score for professional commitment was high(91.37±11.77).A positive correlation was found between critical thinking disposition and professional commitment(r=0.67,P=0.001).Conclusions:Nursing managers are urged to employ strategies to enhance nurses'critical thinking disposition and professional commitment.

关键词： critical thinking nursing education professional commitment skills strategies

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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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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

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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

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Innovative insights into extrachromosomal circular DNAs in gynecologic tumors and reproduction

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Protein & Cell 2024年第1期15卷 6-20页

作者： Ning Wu Ling Wei Zhipeng Zhu Qiang Liu Kailong Li Fengbiao Mao Jie Qiao Xiaolu Zhao State Key Laboratory of Female Fertility Promotion Center for Reproductive MedicineDepartment of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijing 100191China National Clinical Research center for Obstetrics and Gynecology Peking University Third HospitalBeijing 100191China Key Laboratory of Assisted Reproduction(Peking University) Ministry of EducationBeijing 100191China Beijing Key Laboratory of reproductive Endocrinology and Assisted reproductive Technology Beijing 100191China Institute of Medical Innovation and Research Peking University Third HospitalBeijing 100191China Cancer center Peking University Third HospitalBeijing 100191China Department of Biochemistry and Biophysics Beijing Key Laboratory of Protein Posttranslational Modifications and Cell FunctionSchool of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Beijing Advanced Innovation center for Genomics Beijing 100191China Peking-Tsinghua center for Life sciences Peking UniversityBeijing 100191China

Originating but free from chromosomal DNA,extrachromosomal circular DNAs(eccDNAs)are organized in circular form and have long been found in unicellular and multicellular *** biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA,for which few detection methods are *** advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation,evolution,and drug resistance as well as aging,genomic diversity,and other biological processes,bringing it back to the research *** mechanisms of eccDNA formation have been proposed,including the breakage-fusion-bridge(BFB)and translocation-deletion-amplification *** tumors and disorders of embryonic and fetal development are major threats to human reproductive *** roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer *** present review summarized the research history,biogenesis,and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and *** also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection,prognosis,and treatment of gynecologic *** review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.

关键词： extrachromosomal circular DNAs gynecologic tumors reproduction liquid biopsy non-invasive prena-tal testing

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Temperature regulates negative supercoils to modulate meiotic crossovers and chromosome organization

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Science China Life sciences 2024年

作者： Yingjin Tan Taicong Tan Shuxian Zhang Bo Li Beiyi Chen Xu Zhou Ying Wang Xiao Yang Binyuan Zhai Qilai Huang Liangran Zhang Shunxin Wang Research Unit of Gametogenesis and Health of ART-Offspring Chinese Academy of Medical Sciences (No.2021RU001) Advanced Medical Research Institute Shandong University State Key Laboratory of reproductive Medicine and Offspring Health Center for Reproductive Medicine Institute of Women Children and Reproductive Health Shandong University Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology School of Life Sciences Shandong University center for Cell Structure and Function Shandong Provincial Key Laboratory of Animal Resistance Biology College of Life Sciences Shandong Normal University National Research center for Assisted reproductive Technology and reproductive Genetics Shandong University Key Laboratory of reproductive Endocrinology (Shandong University) Ministry of Education Shandong Technology Innovation center for reproductive Health Shandong Provincial Clinical Research center for reproductive Health Shandong Key Laboratory of reproductive Medicine Shandong Provincial Hospital Affiliated to Shandong First Medical University

Crossover recombination is a hallmark of meiosis that holds the paternal and maternal chromosomes(homologs) together for their faithful segregation, while promoting genetic diversity of the progeny. The pattern of crossover is mainly controlled by the architecture of the meiotic chromosomes. Environmental factors, especially temperature, also play an important role in modulating crossovers. However, it is unclear how temperature affects crossovers. Here, we examined the distribution of budding yeast axis components(Red1, Hop1, and Rec8)and the crossover-associated Zip3 foci in detail at different temperatures, and found that both increased and decreased temperatures result in shorter meiotic chromosome axes and more crossovers. Further investigations showed that temperature changes coordinately enhanced the hyperabundant accumulation of Hop1 and Red1 on chromosomes and the number of Zip3 foci. Most importantly, temperature-induced changes in the distribution of axis proteins and Zip3 foci depend on changes in DNA negative supercoils. These results suggest that yeast meiosis senses temperature changes by increasing the level of negative supercoils to increase crossovers and modulate chromosome organization. These findings provide a new perspective on understanding the effect and mechanism of temperature on meiotic recombination and chromosome organization, with important implications for evolution and breeding.

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