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Caseinolytic mitochondrial matrix peptidase X is essential for homologous chromosome synapsis and recombination during meiosis of male mouse germ cells

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Asian Journal of Andrology 2024年第2期26卷 165-174页

作者： Hai-Wei Feng Yu Zhao Yan-Ling Gao Dong-Teng Liu Li-Jun Huo Key Laboratory of Agricultural animal Genetics Breeding and ReproductionEducation Ministry of ChinaCollege of Animal Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China Shenzhen Key Laboratory of Fertility Regulation Reproductive Medicine CenterThe University of Hong Kong-Shenzhen HospitalShenzhen 518053China Maternal-Fetal Medicine Institute Department of Obstetrics and GynaecologyShenzhen Baoan Women's and Children's HospitalJinan UniversityShenzhen 518100China Department of obstetrics and gynaecology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina

Meiosis is the process of producing haploid gametes through a series of complex chromosomal events and the coordinated action of various *** mitochondrial protease complex(ClpXP),which consists of caseinolytic mitochondrial matrix peptidase X(ClpX)and caseinolytic protease P(ClpP)and mediates the degradation of misfolded,damaged,and oxidized proteins,is essential for maintaining mitochondrial *** has been implicated in meiosis regulation,but its precise role is currently *** this study,we engineered an inducible male germ cell-specific knockout caseinolytic mitochondrial matrix peptidase X(Clpx^(cKO))mouse model to investigate the function of ClpX in *** found that disrupting Clpx in male mice induced germ cell apoptosis and led to an absence of sperm in the ***,it caused asynapsis of homologous chromosomes and impaired meiotic recombination,resulting in meiotic arrest in the zygotene-to-pachytene transition *** loss of ClpX compromised the double-strand break(DSB)repair machinery by markedly reducing the recruitment of DNA repair protein RAD51 homolog 1(RAD51)to DSB *** dysfunction may be due to an insufficient supply of energy from the aberrant mitochondria in Clpx^(cKO) spermatocytes,as discerned by electron ***,ubiquitination signals on chromosomes and the expression of oxidative phosphorylation subunits were both significantly attenuated in Clpx^(cKO) *** together,we propose that ClpX is essential for maintaining mitochondrial protein homeostasis and ensuring homologous chromosome pairing,synapsis,and recombination in spermatocytes during meiotic prophase I.

关键词： ClpX homologous chromosome meiosis mitochondrial recombination synapsis

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Attitude and willingness on gamete donation among medical students:An experience from a state university in Sri Lanka

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Asian pacific Journal of reproduction 2024年第3期13卷 120-125页

作者： S.Raguraman K.Muhunthan R.Niroje Department of obstetrics and gynaecology Faculty of MedicineUniversity of JaffnaJaffnaSri Lanka Teaching Hospital Jaffna JaffnaSri Lanka

Objective:To assess the attitude and willingness of medical students of the Faculty of Medicine,University of Jaffna,regarding gamete ***:An institutional-based descriptive cross-sectional study was conducted at the Faculty of Medicine,University of Jaffna,from September 2022 to May 2023 among undergraduate medical students who gave their voluntary participation.A self-administered questionnaire was used as a study instrument to collect data regarding their attitude and willingness toward gamete ***:A total of 345 participants were recruited and their sociodemographic data revealed that 56.8%of the participants were female,62.3%aged between 26 and 30 years,and 92.2%were *** of them received information regarding gamete donations during their clinical *** half(67.8%)of them showed a negative attitude towards gamete *** willingness,only 39.7%of participants had a positive approach for being a gamete donor;among them,84.7%preferred anonymous *** and ethnicity had a significant influence on their attitudes and *** addition,male was also found to be more willing to donate ***:Most medical students have negative views about gamete *** awareness and knowledge of assisted reproductive technology and gamete donation within medical students'sociocultural and ethical backgrounds might facilitate a change in attitude towards gamete donation amongst future medical practitioners.

关键词： Medical students Gamete donation Assisted reproductive technology Attitude Viewpoint

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Rare variants in FANCJ induce premature ovarian insufficiency in humans and mice

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Journal of Genetics and Genomics 2024年第2期51卷 252-255页

作者： Xi Yang Shuting Ren Jialin Yang Yuncheng Pan Zixue Zhou Qing Chen Yunzheng Fang Lingyue Shang Feng Zhang Xiaojin Zhang Yanhua Wu State Key Laboratory of Genetic Engineering at School of Life Sciences Human Phenome InstituteObstetrics and Gynecology HospitalFudan UniversityShanghai 200438China obstetrics and Gynecology Hospital Institute of Reproduction and DevelopmentState Key Laboratory of Genetic Engineering at School of Life SciencesFudan UniversityShanghai 200011China Human Phenome Institute Zhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China obstetrics and Gynecology Hospital Institute of Reproduction and DevelopmentFudan UniversityShanghai 200011China State Key Laboratory of Genetic Engineering at School of Life Sciences Obstetrics and Gynecology HospitalFudan UniversityShanghai 200438China National Demonstration Center for Experimental Biology Education School of Life SciencesFudan UniversityShanghai 200433China

Premature ovarian insufficiency(POI)is a severe female reproductive disorder that affects 1%of women in general populations(European Society for Human reproduction and Embryology[ESHRE]Guideline Group on POI et al.,2016).An increasing prevalence up to 3.7%has been reported in a recent meta-analysis(Golezar et al.,2019).POl can lead to infertility or subfertility,as well as a range of complex complications suffering multi-organ systems,seriously threatening women's health and reducing the life *** contrast,POl is a representative heterogeneous disease with multiple *** more than 70 causative POI genes have been identified,the etiology of more than half of the POI patients is still ambiguous(Jiao et al.,2018).Unreported POI causative genes,therefore,remain to be identified.

关键词： insufficiency fertility

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Patterns of Infertility and Abortion in Saudi Arabia: A Cross-Sectional Study

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Open Journal of obstetrics and Gynecology 2024年第6期14卷 911-922页

作者： Majed Saeed Alshahrani Department of obstetrics and gynaecology College of Medicine Najran University Najran Saudi Arabia

Background: Infertility and abortion are significant reproductive health concerns globally, impacting individuals' well-being and healthcare systems. In Saudi Arabia, cultural, social, and religious factors influence perceptions and management of these issues, necessitating research to understand the patterns and associated factors. Study Aim: This cross-sectional study aimed to investigate the patterns of infertility and abortion among 458 women in Saudi Arabia, focusing on demographic profiles, reproductive histories, medical conditions, and lifestyle factors. Methodology: Participants were recruited from healthcare facilities, and data on age, BMI, reproductive history, medical conditions, assisted reproduction methods, and lifestyle behaviors were collected. Statistical analyses, including chi-square tests, were conducted to examine associations between variables. Results: The majority of participants were aged 30 - 39 years (47.4%), with 76.9% experiencing secondary infertility. Among those with offspring (76.9%), 31% reported using assisted reproduction methods, primarily ovarian stimulators (54.2%). Abortion history was reported by 39.5% of participants. Significant associations were found between age and infertility type (X2 = 5.8, p = 0.054), having offspring and infertility type (X2 = 458.0, p = 0.001), menstrual irregularity and infertility type (X2 = 11.4, p = 0.001), and abortion history and delayed fertility (X2 = 10.4, p = 0.001). Conclusion: Our study reveals significant associations between demographic, medical, and lifestyle factors with infertility patterns and abortion history among Saudi women. These findings emphasize the need for tailored interventions addressing medical conditions, age-related factors, and access to reproductive healthcare services.

关键词： Infertility Abortion Saudi Arabia Reproductive Health Assisted reproduction Cross-Sectional Study

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Subsequent pregnancy outcomes and fertility rates in the case series that underwent bilateral hypogastric artery ligation(BHGAL)due to severe postpartum hemorrhage

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Asian pacific Journal of reproduction 2024年第1期13卷 28-33页

作者： OKUTUCU Gulcan EVSEN Mehmet S PEKER Nurullah YAMAN TUNC Senem ICEN Mehmet S Department of obstetrics and Gynecology Division of PerinatologyTurkish Ministry of Health Ankara City HospitalAnkaraTurkey Department of obstetrics and Gynecology Dicle UniversitySchool of MedicineDiyarbakirTurkey

Objective:To evaluate the effect of bilateral hypogastric artery ligation(BHGAL)on women's pregnancy outcomes and fertility rates in cases with severe postpartum ***:Patients hospitalized in a tertiary care center between 2007 and 2018 were included in the *** records of cases were obtained from the hospital database,*** demographic data,morbidities or complications associated with BHGAL surgery,any additional haemostatic interventional or surgical procedures,preoperative admission and lowest postoperative haematocrit-hemoglobin values,blood products given,type of anaesthesia,intensive care unit(ICU)and length of hospital stay were *** cases without surgical sterilization,future fertility and subsequent pregnancy outcomes were assessed for at least two years after *** was obtained through face-to-face or telephone interviews with patients whose long-term fertility and subsequent pregnancy outcomes were ***:Sixty-eight patients with BHGAL surgery history were included in the study.26 Of 37 cases(70%)that did not undergo surgical sterilization had a desire for pregnancy after the *** of these cases(23%)were diagnosed with secondary *** fertility rate of these cases was 77%,and subsequent pregnancy was detected in 20 women.A total of 25 pregnancies,including first and second pregnancies,developed,and 15 of these pregnancies resulted in term delivery,six preterm births,one stillbirth,and three ***:The postoperative pregnancy rate was found to be higher than the rate of women with infertility problems,and this surgery does not seem to adversely affect pregnancy *** is a tertiary center experience and cohort studies with large patient series are needed.

关键词： Fertility Iliac artery Ligations Postpartum hemorrhage Pregnancy outcomes

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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

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Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress

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Journal of Integrative Medicine 2024年第4期22卷 493-502页

作者： Qian-zhuo Liu Hui Han Xin-ru Fang Lu-yao Wang Dan Zhao Miao-zhu Yin Nian Zhang Peng-yu Jiang Zhi-hui Ji Li-min Wu Department of Neurology the First Affiliated Hospital of Anhui University of Chinese MedicineHefei 230031Anhui ProvinceChina Center for reproduction and Genetics the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230031Anhui ProvinceChina

Objective:Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for ***:Mice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe2+) and trivalent iron (Fe3+) levels, as well as malondialdehyde (MDA), glutathione(GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) ***:Ovarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine,a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron,Fe2+, MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4)expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) ***:Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress.

关键词： Berberine Hepatolenticular degeneration Copper deposition Ferroptosis Endoplasmic reticulum stress

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Knowledge, attitudes, and practices regarding Covid-19 and their relationship with Covid-19 booster vaccination status among women with infertility

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Asian pacific Journal of reproduction 2024年第2期13卷 68-75页

作者： Gita Pratama Mila Maidarti Kanadi Sumapradja Achmad Kemal Harzif Natasha Talya Kevin Ezekia Irfan Arieqal Hatta Ampri Reproductive Immunoendocrinology division Department of Obstetrics and GynecologyFaculty of Medicine Universitas Indonesia-dr.Cipto Mangunkusumo General HospitalJakartaIndonesia Yasmin IVF Clinic dr.Cipto Mangunkusumo General Hospital JakartaIndonesia Human reproduction Infertilityand Family Planning ClusterIndonesia Reproductive Medicine Research and Training CenterFaculty of MedicineUniversitas IndonesiaJakarta 10430Indonesia Department of obstetrics and Gynecology Faculty of Medicine Universitas Indonesia-dr.Cipto Mangunkusumo General HospitalJakartaIndonesia

Objective:To elucidate the relationship among knowledge,attitudes,and practices regarding Covid-19 and their relationship with booster vaccination status among women with ***:This questionnaire-based cross-sectional study was performed online and offline among women with infertility who visited an infertility clinic in Jakarta,*** assessed the patient’s knowledge,attitudes,and practices regarding Covid-19 and their relationship with booster vaccination status and sociodemographic ***:A total of 178 subjects participated in this study,and most participants(92.6%)had received booster Covid-19 *** the questionnaire,74.2%had good knowledge,and 99.4%had good attitudes regarding Covid-19;however,only 57.9%of patients had good practices.A weak positive correlation existed between knowledge and attitudes(r=0.11,P=0.13)and a moderate negative correlation between attitudes and practices(r=-0.44,P=0.56).Participants’knowledge about vaccines and infertility was correlated with booster vaccination status(P=0.04).Academic background(P=0.01)and attitudes(P=0.01)were also correlated with booster vaccination *** significant determinants of hesitance of receiving Covid-19 booster vaccines were high school education or below(OR=0.08,95%CI 0.02-0.36)and poor practices(OR=0.21,95%CI 0.05-0.95).Conclusions:The majority of the participants had received the Covid-19 booster vaccine and had good knowledge and attitudes but poor practices regarding *** participants had poor knowledge about the relationship between infertility and the Covid-19 *** general population should be more informed and reminded about practices to prevent Covid-19 and the relationship between vaccination and fertility to increase the number of people who receive Covid-19 booster vaccines.

关键词： Covid-19 Booster vaccine Infertility Knowledge Attitude Practice Human reproduction Pandemic

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Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

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Journal of Pharmaceutical Analysis 2024年第1期14卷 100-114页

作者： Sze Wan Hung Massimiliano Gaetani Yiran Li Zhouyurong Tan Xu Zheng Ruizhe Zhang Yang Ding Gene Chi Wai Man Tao Zhang Yi Song Yao Wang Jacqueline Pui Wah Chung Tak Hang Chan Roman A.Zubarev Chi Chiu Wang Department of obstetrics&gynaecology The Chinese University of Hong KongHong KongChina division of Physiological Chemistry I Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Chemical Proteomics Core Facility Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Unit of Chemical Proteomics Science for Life Laboratory(SciLifeLab)StockholmSE 17177Sweden Center for Reproductive Medicine Henan Key Laboratory of Reproduction and GeneticsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450003China Department of Chemistry McGill UniversityMontrealH3A2K6Canada Department of Pharmacological&Technological Chemistry I.M.Sechenov First Moscow State Medical UniversityMoscow119146Russia reproduction and Development Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine The Chinese University of Hong KongHong KongChina

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the *** is a major pathophysiology in *** previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain *** this study,we demonstrated that oral ProEGCG can be effective in preventing and treating ***,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,*** simulation and BioLayer interferometry were used to confirm their binding *** results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)*** vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling ***,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

关键词： Molecular targets ProEGCG EGCG Angiogenesis Treatment Endometriosis

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A mutation in TBXT causes congenital vertebral malformations in humans and mice

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Journal of Genetics and Genomics 2024年第4期51卷 433-442页

作者： Shuxia Chen Yunping Lei Yajun Yang Chennan Liu Lele Kuang Li Jin Richard HFinnell Xueyan Yang Hongyan Wang obstetrics and Gynecology Hospital State Key Laboratory of Genetic Engineering at School of Life SciencesKey Laboratory of Reproduction Regulation of NPFPCInstitute of Reproduction and DevelopmentFudan UniversityShanghai 200438China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Center for Precision Environmental Health Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonTX 77030USA MOE Key Laboratory of Contemporary Anthropology School of Life SciencesFudan UniversityShanghai 200438China Department of Assisted reproduction Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China Children’s Hospital Fudan University399 Wanyuan RoadShanghai 201102China

T-box transcription factor T(TBXT;T)is required for mesodermal formation and axial skeletal *** it has been extensively studied in various model organisms,human congenital vertebral malformations(CVMs)involving T are not well ***,we report a family with 15 CVM patients distributed across 4 *** affected individuals carry a heterozygous mutation,T c.596A>G(p.Q199R),which is not found in unaffected family members,indicating co-segregation of the genotype and *** vitro assays show that T p.Q199R increases the nucleocytoplasmic ratio and enhances its DNA-binding affinity,but reduces its transcriptional activity compared to the *** determine the pathogenicity of this mutation in vivo,we generated a Q199R knock-in mouse model that recapitulates the human CVM *** heterozygous Q199R mice show subtle kinked or shortened tails,while homozygous mice exhibit tail filaments and severe vertebral ***,we show that the Q199R mutation in T causes CVM in humans and mice,providing previously unreported evidence supporting the function of T in the genetic etiology of human CVM.

关键词： Congenital vertebral malformation TBXT T gene Loss-of-function mutation

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