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Asian Journal of Andrology 2024年第2期26卷 183-188页

作者： Huan Jiang Chu-Jie Huang Department of reproductive endocrinology Longgang District Maternity&Child Healthcare Hospital of Shenzhen City(Longgang Maternity and Child Institute of Shantou University Medical College)Shenzhen 518172China Institute of reproductive Immunology College of Life Science and TechnologyJinan UniversityGuangzhou 510632China

Aberrant sperm protamination is linked to sperm dysmorphology and nuclear chromatin ***,its effects on sperm cytoplasmic maturation remain largely *** relationships of protamines,sperm morphology,DNA damage,and cytoplasmic remodeling were illustrated in this study to provide fresh perspectives on the mechanisms of male infertility.A total of 205 infertile males were allocated into 5 groups according to the percentage of spermatozoa exhibiting abnormal morphology within their *** concentration,motility,abnormal sperm morphology,cytoplasmic droplets(CDs),and excess residual cytoplasm(ERC)were analyzed according to the World Health Organization manual(2010).Sperm nuclear vacuoles(NVs)were determined by propidium iodide(PI)*** protamine expressions(P1 and P2)were detected by western *** damage was measured by acridine orange test(AOT)to calculate the proportion of sperm with single-strand DNA breaks(SSBs).Our data showed that sperm concentration and motility in infertile males significantly decreased with the severity of abnormal sperm morphology(both P<0.01).P1 level,P1/P2 ratio,and SSB rate increased with the severity of sperm dysmorphology,whilst the P2 level decreased(all P

关键词： abnormal sperm morphology excess residual cytoplasm male infertility protamines sperm DNA damage sperm nuclear vacuoles

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

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

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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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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Molybdenum Concentration and the Risk of Spontaneous Preterm Birth: A Nested Case-Control Study — Beijing Municipality, China, 2018–2020

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China CDC weekly 2024年第13期6卷 261-266,I0005,I0006页

作者： Junhua Huang Wei Zheng Aili Wang Weiling Han Junxi Chen Hang An Lailai Yan Zhiwen Li Guanghui Li division of endocrinology and Metabolism Department of ObstetricsBeijing Obstetrics and Gynecology HospitalCapital Medical University.Beijing Maternal and Child Health Care HospitalBeijingChina Department of Obstetrics and Gynecology Beijing Luhe HospitalCapital Medical UniversityBeijingChina Institute of reproductive and Child Health National Health Commission Key Laboratory of Reproductive HealthPeking UniversityBeijingChina Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijingChina Department of Laboratorial Science and Technology School of Public HealthPeking UniversityBeijingChina

What is already known about this topic?The level of molybdenum(Mo)in a mother’s urine has been linked to the growth rate of the fetus and the blood pressure levels in *** is added by this report?We evaluated the variations in maternal plasma Mo concentrations throughout pregnancy and their potential association with the risk of spontaneous preterm birth(SPB).What are the implications for public health practice?Future research must determine the Mo levels in pregnant women across various regions in ***,particular attention needs to be given to the potential increase in Mo concentration throughout pregnancy and its possible adverse impacts on the health of both the mother and the fetus.

关键词： mother urine pregnancy

Deleterious variants in RNF111 impair female fertility and induce premature ovarian insufficiency in humans and mice

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Science China(Life Sciences) 2024年第7期67卷 1325-1337页

作者： Chengcheng Song Yingying Qin Yan Li Bingyi Yang Ting Guo Wenqing Ma Dian Xu Keyan Xu Fangfang Fu Li Jin Yanhua Wu Shuyan Tang Xiaojun Chen Feng Zhang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic EngineeringInstitute of Medical Genetics and GenomicsFudan UniversityShanghai 200011China Human Phenome Institute Zhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China Center for reproductive Medicine Cheeloo College of MedicineShandong UniversityJinan 250021China State Key Laboratory of reproductive Medicine and Offspring Health Key Laboratory of Reproductive Endocrinology of Ministry of EducationNational Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthShandong UniversityJinan 250021China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China National Demonstration Center for Experimental Biology Education School of Life SciencesFudan UniversityShanghai 200433China Department of Gynecology the Tenth People’s Hospital of Tongji UniversityShanghai 200072China Soong Ching Ling Institute of Maternity and Child Health International Peace Maternity and Child Health Hospital of China Welfare InstituteShanghai 200030China

Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of *** represents a significant detriment to female ***,the known POI-causative genes currently account for only a fraction of *** 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 *** 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 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 ***,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling *** analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and *** 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 ***,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 *** conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.

关键词： POI RNF111 female fertility ovarian reserve

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Development and validation of a novel non-invasive test for diagnosing nonalcoholic fatty liver disease in Chinese children

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World Journal of Pediatrics 2024年第4期20卷 413-421页

作者： Zhe-Wen Qin Qian-Nan Ren Hong-Xi Zhang Ya-Ru Liu Ke Huang Wei Wu Guan-Ping Dong Yan Ni Jun-Fen Fu division of endocrinology National Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalDepartment of EndocrinologyNational Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalZhejiang University School of MedicineHangzhou310052China

With the exploding prevalence of obesity,many children are at risk of developing nonalcoholic fatty liver *** anthropometric and laboratory parameters,our study aimed to develop a model to quantitatively evaluate liver fat content(LFC)in children with *** A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the endocrinology Department as the derivation *** external validation cohort comprised 77 *** assessment of liver fat content was performed using proton magnetic resonance *** and laboratory metrics were measured in all subjects.B-ultrasound examination was carried out in the external validation *** Kruskal-Wallis test,Spearman bivariate correlation analyses,univariable linear regressions and multivariable linear regression were used to build the optimal predictive *** The model was based on indicators including alanine aminotransferase,homeostasis model assessment of insulin resistance,triglycerides,waist circumference and Tanner *** adjusted R^(2)of the model was 0.589,which presented high sensitivity and specificity both in internal[sensitivity of 0.824,specificity of 0.900,area under curve(AUC)of 0.900 with a 95%confidence interval:0.783–1.000]and external validation(sensitivity of 0.918 and specificity of 0.821,AUC of 0.901 with a 95%confidence interval:0.818–0.984).Conclusions Our model based on five clinical indicators was simple,non-invasive,and inexpensive;it had high sensitivity and specificity in predicting LFC in ***,it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.

关键词： Biochemical markers Children Magnetic resonance spectroscopy Nonalcoholic fatty liver disease Pediatric obesity

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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Glucagon-like peptide-1 receptor agonists as a possible intervention to delay the onset of type 1 diabetes:A new horizon

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World Journal of Diabetes 2024年第2期15卷 133-136页

作者： Mahmoud Nassar Ajay Chaudhuri Husam Ghanim Paresh Dandona Department of Internal Medicine Division of EndocrinologyDiabetes and MetabolismJacobs School of Medicine and Biomedical SciencesUniversity of BuffaloBuffaloNY 14221United States

Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and *** management of T1D primarily focuses on exogenous insulin replacement to control blood glucose ***,this approach does not address the underlying autoimmune process or prevent the progressive loss of beta *** research has explored the potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)as a novel intervention to modify the disease course and delay the onset of ***-1RAs are medications initially developed for treating type 2 *** exert their effects by enhancing glucose-dependent insulin secretion,suppressing glucagon secretion,and slowing gastric *** evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with *** article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D,possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of *** article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification,which should open new avenues for preventing and treating T1D,improving the quality of life and long-term outcomes for individuals at risk of T1D.

关键词： Type 1 diabetes Semaglutide Glucagon-like peptide-1 receptor agonists Insulin therapy Autoimmune response Blood glucose monitoring Β-cell preservation Early screening Teplizumab Randomized controlled trials