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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

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

Association between MTHFR c.677C>T variant and erectile dysfunction among males attending fertility clinic

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Asian Journal of Andrology 2024年第1期26卷 41-45页

作者： Shun Bai Ming-Zhen Li Yang-Yang Wan Xue-Chun Hu Yi-Xun Liu Xian-Hong Tong Tong-Hang Guo Lu Zong Ran Liu Yuan-Qi Zhao Ping Xiang Bo Xu Xiao-Hua Jiang Department of Gynecology and Obstetrics Reproductive and Genetic HospitalThe First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China NHC Key laboratory of male Reproduction and Genetics Guangdong Provincial Reproductive Science Institute(Guangdong Provincial Fertility Hospital)Guangzhou 510600China Department of Urology The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Wannan Medical College Wuhu 241002China

Genetic risk factors have been shown to contribute to the development of sexual ***,the role of methylenetetrahydrofolate reductase(MTHFR)gene variants in the risk of erectile dysfunction(ED)remains *** this study,we recruited 1254 participants who underwent ED assessed by the International Index of Erectile *** MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction(PCR).No significant difference in the genotypic frequency of the MTHFR C677T polymorphism(CC,CT,and TT)was observed between men from the ED and non-ED *** addition,on binary logistic regression analysis,both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T ***,a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED(P=O.02).The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis,even after adjusting for potential confounders(odds ratio[OR]=2.46,95%confidence interval[CI]:1.15-5.50,P=0.02).These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe *** of MTHFR gene polymorphisms may provide complementary information for ED patients during routineclinicaldiagnosis.

关键词： erectile dysfunction gene variant genetic risk factors methylenetetrahydrofolate reductase sexual function

Sex differences in human pre-gastrulation embryos

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Science China Life Sciences 2024年

作者： Yongjie Lu Meng Qin Xintong Qi Ming Yang Fan Zhai Jiaqi Zhang Zhiqiang Yan Liying Yan Jie Qiao Peng Yuan State Key laboratory of Female Fertility Promotion Center for Reproductive Medicine Department of Obstetrics and Gynecology Peking University Third Hospital National Clinical research Center for Obstetrics and Gynecology (Peking University Third Hospital) Key laboratory of Assisted Reproduction (Peking University) Ministry of Education Beijing Key laboratory of reproductive Endocrinology and Assisted reproductive Technology Academy for Advanced Interdisciplinary Studies Peking University

Human fetuses exhibit notable sex differences in growth rate and response to the intrauterine environment, yet their origins and underlying mechanisms remain uncertain. Here, we conduct a detailed investigation of sex differences in human pre-gastrulation embryos. The lower methylation and incomplete inactivation of the X chromosome in females, as well as the sex-specific cell-cell communication patterns,contribute to sex-differential transcription. male trophectoderm is more inclined toward syncytiotrophoblast differentiation and exhibits a stronger hormone secretion capacity, while female trophectoderm tends to retain cytotrophoblast program with stronger mitochondrial function as well as higher vasculogenesis and immunotolerance signals. male primitive endoderm initiates the anterior visceral endoderm transcriptional program earlier than females. The cell cycle activities of the epiblast and primitive endoderm are higher in males compared to females, while the situation is opposite in the trophectoderm. In conclusion, our study provides in-depth insights into the sex differences in human pre-gastrulation embryos and contributes to unraveling the origins of the sex differences in human fetal development.

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Preimplantation genetic testing for aneuploidy could not improve cumulative live birth rate among 1003 couples with recurrent pregnancy loss

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中华医学杂志(英文版) 2024年第17期137卷 2024 Apr 17页

作者： Zhao Shaotong Lyu Chunzi Liu Yingbo Wang Xiyao Zhang Zhaowen Lv Hong Ni Tianxiang Yan Junhao Center for reproductive Medicine Shandong University Jinan Shandong China Key laboratory of reproductive Endocrinology of Ministry of Education Shandong University Jinan Shandong China Shandong Key laboratory of reproductive Medicine Jinan Shandong China Shandong Provincial Clinical research Center for reproductive Health Jinan Shandong China Shandong Technology Innovation Center for reproductive Health Jinan Shandong China National research Center for Assisted reproductive Technology and reproductive Genetics Shandong University Jinan Shandong China

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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reproductive and Developmental Medicine 2024年第1期8卷 1-7页

作者： Qing Zhao Jie Li Wei-Lin Wang Ying-Bo Liu Jing Li Tian-Xiang Ni Wei Zhou Qian Zhang Jun-Hao Yan Center for reproductive Medicine Shandong UniversityJinan 250012China State Key laboratory of reproductive Medicine and Offspring Health Shandong UniversityJinan 250012China Key laboratory of reproductive Endocrinology of Ministry of Education Shandong UniversityJinan 250012China Shandong Key laboratory of reproductive Medicine Jinan 250012China Shandong Provincial Clinical research Center for reproductive Health Jinan 250012China Shandong Technology Innovation Center for reproductive Health Jinan 250012China National research Center for Assisted reproductive Technology and reproductive Genetics Shandong UniversityJinan 250012China

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 *** 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,***:1.119,0.660–1.896,P=0.677;***: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

Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella(MMAF)and ICSI outcomes

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Asian Journal of Andrology 2024年第1期26卷 91-98页

作者： Zhong-Mei Shao Yu-Tong Zhu Meng Gu Sen-Chao Guo Hui Yu Kuo-Kuo Li Dong-Dong Tang Yu-Ping Xu Ming-Rong Lv reproductive Medicine Center Department of Obstetrics and Gynecologythe First Affiliated Hospital of Anhui Medical UniversityHefei 230022China Department of Obstetrics and Gynecology Fuyang Hospital of Anhui Medical UniversityFuyang 236112China 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'sRepublicof ChinaHefei 230032China

Variations in the dynein axonemal heavy chain gene,dynein axonemal heavy chain 6(DNAH6),lead to multiple morphological abnormalities of the *** studies have reported that these deficiencies may result in sperm head ***,whether DNAH6 is also involved in human acrosome biogenesis remains *** purpose of this study was to investigate DNAH6 gene variants and their potential functions in the formation of defective sperm heads and ***-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University(Hefei,China).Hematoxylin and eosin staining,scanning electron microscopy,and transmission electron microscopy were performed to analyze the sperm morphology and *** staining and Western blot analysis were conducted to examine the effects of genetic *** identified three novel deleterious variants in DNAH6 among three unrelated *** absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 ***,deficiencies in the acrosome,abnormal chromatin compaction,and vacuole-containing sperm heads were observed in these patients with DNAH6 *** decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western *** intracytoplasmic sperm injection(ICSl)treatment,the partner of one patient with a DNAH6 variant achieved successful ***,novel variants in DNAH6 genes that contribute to defects in the sperm head and flagella were identified,and the findings indicated Icsl as an effective clinical treatment for such patients.

关键词： asthenoteratospermia DNAH6 intracytoplasmic sperm injection male infertility

Germ cell-specific deletion of Pex3 reveals essential roles of PEX3-dependent peroxisomes in spermiogenesis

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The Journal of Biomedical research 2024年第1期38卷 24-36页

作者： Yejin Yao Baolu Shi Xiangzheng Zhang Xin Wang Shuangyue Li Ying Yao Yueshuai Guo Dingdong Chen Bing Wang Yan Yuan Jiahao Sha Xuejiang Guo State Key laboratory of reproductive Medicine and Offspring Health Nanjing Medical UniversityNanjingJiangsu 211166China reproductive and Genetic Branch the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China State Key laboratory of reproductive Medicine and Offspring Health Women's Hospital of Nanjing Medical UniversityNanjing Maternity and Child Health Care HospitalNanjing Medical UniversityNanjingJiangsu 211166China.

Peroxisomes are organelles enclosed by a single membrane and are present in various *** abruption of peroxisomes is correlated with peroxisome biogenesis disorders and single peroxisomal enzyme deficiencies that induce diverse diseases in different ***,little is known about the protein compositions and corresponding roles of heterogeneous peroxisomes in various *** transcriptomic and proteomic analyses,we observed heterogenous peroxisomal components among different organs,as well as between testicular somatic cells and different developmental stages of germ *** Pex3 is expressed in both germ cells and Sertoli cells,we generated Pex3 germ cell-and Sertoli cell-specific knockout *** Pex3 deletion in Sertoli cells did not affect spermatogenesis,the deletion in germ cells resulted in male sterility,manifested as the destruction of intercellular bridges between spermatids and the formation of multinucleated giant *** analysis of the Pex3-deleted spermatids revealed defective expressions of peroxisomal proteins and spermiogenesis-related *** findings provide new insights that PEX3-dependent peroxisomes are essential for germ cells undergoing spermiogenesis,but not for Sertoli cells.

关键词： male infertility spermiogenesis peroxisome oxidative stress PEX3

A novel preimplantation genetic testing strategy for a subtelomeric genetic disorder:A case study

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Genes & Diseases 2024年第4期11卷 13-15页

作者： Songchang Chen Li Wanng Luting Chen Weihui Shi Junyu Zhang Yuting Hu Yinyu Wang Li Jin Jianzhong Sheng Feng Zhang Yanting Wu Hefeng Huang Chenming Xu Obstetrics and Gynecology Hospital Institute of Reproduction and DevelopmentFudan UniversityShanghai 200090China The International Peace Maternity and Child Health Hospital School of MedicineShanghai Jiao Tong UniversityShanghai 200030China research Units of Embryo Original Diseases Chinese Academy of Medical SciencesShanghai 200030China Key laboratory of reproductive Genetics(Ministry of Education) Department of Reproductive EndocrinologyWomen's HospitalZhejiang University School of MedicineHangzhouZhejiang 310058China Shanghai Key laboratory of Embryo Original Diseases Shanghai 200030China Shanghai First Maternity and Infant Hospital Tongji University School of MedicineShanghai 200030China

Preimplantation genetic testing(PGT)is a precise and effective technique for detecting inherited pathogenic mutations to prevent birth ***,there are few reports on PGT for pseudo-autosomal genetic diseases.

关键词： implantation testing precise