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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

Viral-mediated gene therapy in pediatric neurological disorders

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World Journal of Pediatrics 2024年第6期20卷 533-555页

作者： Jing Peng Wei-Wei Zou Xiao-Lei Wang Zhi-Guo Zhang Ran Huo Li Yang department of Pediatrics Clinical Research Center for Chidren Neurodevelopmental disablities of Hunan ProvinceXiangya HospitalCentral South UniversityChangsha 410008China reproductive medicine center Department of Obstetrics and Gynecologythe First Affiliated Hospital of Anhui Medical UniversityHefeiChina State Key Laboratory of reproductive medicine Nanjing Medical UniversityNanjingChina

Background Due to the broad application of next-generation sequencing,the molecular diagnosis of genetic disorders in pediatric neurology is no longer an unachievable ***,treatments for neurological genetic disorders in children remain primarily *** the other hand,with the continuous evolution of therapeutic viral vectors,gene therapy is becoming a clinical *** this perspective,we wrote this review to illustrate the current state regarding viral-mediated gene therapy in childhood neurological *** sources We searched databases,including PubMed and Google Scholar,using the keywords"adenovirus vector,""lentivirus vector,"and"AAv"for gene therapy,and"immunoreaction induced by gene therapy vectors,""administration routes of gene therapy vectors,"and"gene therapy"with"NCL,""SMA,""DMD,""congenital myopathy,""MPS""leukodystrophy,"or"pediatric metabolic disorders".We also screened the database of *** using the keywords"gene therapy for children"and then filtered the results with the ones aimed at neurological *** time range of the search procedure was from the inception of the databases to the *** We presented the characteristics of commonly used viral vectors for gene therapy for pediatric neurological disorders and summarized their merits and drawbacks,the administration routes of each vector,the research progress,and the clinical application status of viral-mediated gene therapy on pediatric neurological *** Viral-mediated gene therapy is on the brink of broad clinical ***-mediated gene therapy will dramatically change the treatment pattern of childhood neurological disorders,and many children with incurable diseases will meet the dawn of a ***,the vectors must be optimized for better safety and efficacy.

关键词： Gene therapy Neurological disorders Pediatrics Viral vectors

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

Association between body mass index and in vitro fertilization/intra-cytoplasmic sperm injection outcomes:An analysis of 15,124 normal ovarian responders in China

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Chinese Medical Journal 2024年第7期137卷 837-845页

作者： Danlei Zheng Yuanyuan Wang Lixue Chen Lin Zeng Rong Li department of Obstetrics and Gynecology Center for Reproductive MedicinePeking University Third HospitalBeijing 100191China Research center of Clinical Epidemiology Peking University Third HospitalBeijing 100191China

Background:High body mass index(BMI)results in decreased fecundity,and women with high BMI have reduced rates of clinical pregnancy and live birth in in vitro fertilization/intra-cytoplasmic sperm injection(IVF/ICSI).Meanwhile,ovarian responses show great heterogeneity in patients with a high *** study aimed to analyze the effects of a high BMI on IVF/ICSI outcomes in the Chinese female with normal ovarian ***:We performed a retrospective cohort study comprising 15,124 patients from the medical record system of the reproductive center of Peking University Third Hospital,with 3530(23.3%)in the overweight group and 1380(9.1%)in the obese group,who had a normal ovarian response(5-15 oocytes retrieved)and underwent fresh embryo transfer(ET)cycles from January 2017 to December 2018,followed by linked frozen-thawed embryo transfer(FET)cycles from January 2017 to December *** live birth rate(CLBR)was used as the primary ***,a generalized additive model was applied to visually illustrate the curvilinear relationship between BMI and the *** used a decision tree to identify the specific population where high BMI had the greatest effect on IVF/ICSI ***:High BMI was associated with poor IVF/ICSI outcomes,both in cumulative cycles and in separate fresh ET or FET *** cumulative cycles,compared with the normal weight group,obesity was correlated with a lower positive pregnancy test rate(adjusted odds ratio[aOR]:0.809,95%confidence interval[CI]:0.682-0.960),lower clinical pregnancy rate(aOR:0.766,95%CI:0.646-0.907),lower live birth rate(aOR:0.706,95%CI:0.595-0.838),higher cesarean section rate(aOR:2.066,95%CI:1.533-2.785),and higher rate of large for gestational age(aOR:2.273,95%CI:1.547-3.341).In the generalized additive model,we found that CLBR declined with increasing BMI,with 24 kg/m^(2)as an inflection *** the decision tree,BMI only made a difference in the population aged≤34.5 years,with anti-Muller

关键词： Obesity Body mass index fertilization Live birth Decision trees Normal ovarian response

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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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

Artificial intelligence system for outcome evaluations of human in vitro fertilization-derived embryos

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中华医学杂志(英文版) 2024年第16期137卷 2024 Jul 12页

作者： Sun Ling Li Jiahui Zeng Simiao Luo Qiangxiang Miao Hanpei Liang Yunhao Cheng Linling Sun Zhuo Tai Wa Hou Han Yibing Yin Yun Wu Keliang Zhang Kang department of reproductive medicine Guangzhou Women and Children’s Medical Center Guangzhou Medical University Guangzhou Guangdong China Guangzhou National Laboratory Guangzhou Guangdong China department of reproductive medicine Jiangmen Central Hospital Jiangmen Guangdong China department of Ophthalmology Dongguan People’s Hospital The First School of Clinical Medicine Southern Medical University Dongguan Guangdong China Institute for Artificial Intelligence in medicine Faculty of Medicine Macau University of Science and Technology Macau Special Administrative Region China Wenzhou Eye Hospital Institute for Advanced Studies on Eye Health and Diseases Wenzhou Medical University Wenzhou Zhejiang China Kiang Wu Hospital Macau Special Administrative Region China Faculty of Business City University of Macau Macau Special Administrative Region China State Key Laboratory of reproductive medicine and Offspring Health Center for Reproductive Medicine Institute of Women Children and Reproductive Health and Key laboratory of Reproductive Endocrinology of Ministry of Education Shandong University Jinan Shandong China

Background: In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly ***: We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth ***: These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1%vs. 30.7% on day 3, 55.0%vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidenc

关键词： Artificial intelligence Fertilizationin vitro Embryo implantation Blastocyst Aneuploidy Neural networks, computer Live birth

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