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Chinese Medical Journal 2023年第4期136卷 499-501页

作者： Jiaqi Chang Lihong Xu Yiming Qin Ran Liu Chenxi Li Shanshan Gao Yujie Dang center for reproductive Medicine Key Laboratory of Reproductive Endocrinology of Ministry of EducationShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthNational Research Center for Assisted Reproductive Technology and Reproductive GeneticsCheeloo College of MedicineShandong UniversityJinanShandong 250012China Department of Gynaecology and Obstetrics Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250021China shandong First Medical University JinanShandong 250021China

To the Editor:Infertility affects 15%to 20%of couples worldwide,and assisted reproductive technology(ART)is the most effective treatment strategy.In addition to female age,many other factors,such as antral follicle count(AFC),basal follicle-stimulating hormone(FSH)level,and anti-Mullerian hormone(AMH)level,collectively known as biomarkers for ovarian reserve tests(ORTs),are widely used to predict ovarian responses and assisted-pregnancy outcomes.[1]Among them,AMH and FSH levels were discordant in 20%to 43%of women undergoing ART treatment,and AMH was proven to be superior in predicting live birth rate(LBR).[2]

关键词： pregnancy collective treatment

The effect of SARS-CoV-2 infection on human embryo early development:a multicenter prospective cohort study

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Science China(Life Sciences) 2023年第7期66卷 1697-1700页

作者： Xiaolei Chen Huangcong Shi Cheng Li Wanxia Zhong Linlin Cui Wenjun Zhang Ling Geng Kuona Hu Mei Fang Daimin Wei Junhao Yan Yun Sun Keliang Wu Han Zhao Zi-Jiang Chen center for reproductive Medicine Shandong UniversityJinan 250012China research Unit of Gametogenesis and health of ART-Offspring Chinese Academy of Medical SciencesJinan 250012China Key Laboratory of reproductive Endocrinology of Ministry of Education Shandong UniversityShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthJinan 250012China National research center of Assisted reproductive Technology and reproductive Genetics Shandong UniversityJinan 250012China center for reproductive Medicine The Second HospitalCheeloo College of MedicineShandong UniversityJinan 250012China center for reproductive medicine Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Key Laboratory for Assisted Reproduction and Reproductive GeneticsShanghai 200127China

Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection has swept the globe for 3 years(Zhou et al.,2020).With the nationwide relaxation of controls on the coronavirus disease 2019(COVID-19)epidemic since December 2022 in China,fertility and in vitro fertilization(IVF)centers are receiving increasing numbers of infected patients.

关键词： infection acute

A new TEX11 mutation causes azoospermia and testicular meiotic arrest

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Asian Journal of Andrology 2021年第5期23卷 510-515页

作者： Xiao-Chen Yu Meng-Jing Li Fei-Fei Cai Si-Jie Yang Hong-Bin Liu Hao-Bo Zhang center for reproductive Medicine Cheeloo College of MedicineShandong 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 25CX312China National research center for Assisted reproductive Technology and reproductive Genetics Shandong UniversityJinan 250012China

There are many unknown genetic factors that lead to infertility in nonobstructive azoospermia men.Here,we performed whole-exome sequencing in blood samples obtained from 40 azoospermia patients with meiotic arrest and found a novel c.151_154del(p.D51fs)frame-shift mutation in exon 3 of the testis expressed 11(TEX11)gene in one patient.Sanger sequencing analysis of the patient and 288 fertile men was performed to validate the mutation.Immunohistochemical analysis showed TEX11 expression in late-pachytene spermatocytes and in round spermatids in fertile human testes.In contrast,testes of the patient with TEX11 mutation underwent meiotic arrest and lacked TEX11 expression.Western blotting of human embryonic kidney(HEK293)cells transfected with a vector for the p.D51fs TEX11 variant detected no TEX11 expression.In conclusion,we identified a novel frame-shift mutation in the TEX11 gene in an azoospermia patient,emphasizing that this gene should be included in genetic screening panels for the clinical evaluation of azoospermia patients.

关键词： male infertility meiotic arrest nonobstructive azoospermia testis expressed 11

电热损伤法建立新西兰大白兔宫腔粘连模型（英文）

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2018年第5期19卷 383-389页

作者： Xin-xin XU Lian-bao CAO Zhe WANG Zhen XU Bing-qian ZHANG She-ling WU Sha-sha QI Lei YAN Zi-jiang CHEN center for reproductive Medicine Shandong Provincial Hospital Affiliated to Shandong University/National Research Center for Assisted Reproductive Technology and Reproductive Genetics/MOE Key Laboratory of Reproductive Endocrinology (Shandong University)/Shandong Provincial Key Laboratory of Reproductive Medicine center for reproductive Medicine the Fifth People’s Hospital of Jinan

目的:目前宫腔粘连(Intrauterine adhesion,IUA)发病机制及治疗方法仍未明确和统一,建立一个稳定有效的宫腔粘连动物模型是开展相关研究的前提和基础。本文旨在利用电热损伤法构建兔IUA模型,观察和评估该方法的建模效果。创新点:首次提... 详细信息

目的:目前宫腔粘连(Intrauterine adhesion,IUA)发病机制及治疗方法仍未明确和统一,建立一个稳定有效的宫腔粘连动物模型是开展相关研究的前提和基础。本文旨在利用电热损伤法构建兔IUA模型,观察和评估该方法的建模效果。创新点:首次提出利用电热损伤法建立兔宫腔粘连模型,并得出在损伤后7~14天内建立的兔IUA模型是有效的结论。方法:将21只成年雌性新西兰大白兔一侧子宫内膜用医用多功能高频电刀电灼损伤模拟宫腔粘连形成(A组,n=21),另一侧子宫不做处理作为自身对照(B组,n=21)。分别在损伤后7、14和28天收集兔双侧子宫组织,行苏木精-伊红染色法(HE)和Masson染色观察两侧子宫内膜病理改变,并对两侧子宫内膜的腺体个数和内膜纤维化面积比进行统计学分析和比较。另外,将损伤后7天的雌兔与成年雄兔合笼,14天后观察比较两侧子宫胚胎个数。结论:病理组织学观察显示,损伤后7和14天,A组子宫内膜腺体数量较B组减少,差异均有统计学意义(P<0.05);而损伤后30天,A组子宫内膜腺体数量与B组相比差异无统计学意义。损伤后7天,A组内膜纤维化面积较B组增大,差异有统计学意义(P<0.01);A组子宫胚胎个数较B组减少,差异有统计学意义(P<0.01)。综上所述,采用电热损伤法建立的兔宫腔粘连模型在损伤后7~14天是稳定有效的。

关键词：宫腔粘连电热损伤兔模型

Effect of orlistat on obese women with polycystic ovary syndrome

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Journal of Bio-X research 2018年第3期1卷 128-131页

作者： Qi Jiang Yuhua Shi center for reproductive Medicine Shandong UniversityNational Research Center for Assisted Reproductive Technology and Reproductive Geneticsthe Key Laboratory for Reproductive Endocrinology of Ministry of EducationShandong Provincial Clinical Medicine Research Center for Reproductive HealthJinanShandong ProvinceChina

Polycystic ovary syndrome(PCOS)is a common gynecological endocrine syndrome characterized by metabolic abnormality and reproductive dysfunction,including ovulation abnormality,hyperandrogenism and polycystic ovarian manifestations.Most PCOS patients are overweight or obese,particularly the central type.This aggravates the clinical manifestations of PCOS and ultimately increases the risk of infertility.Orlistat is the only weight loss drug approved by the US Food and Drug Administration.As a long-lasting gastrointestinal lipase inhibitor,orlistat can effectively reduce the absorption of lipid and increase lipid excretion,thereby achieving weight loss.In obese PCOS patients,orlistat can reduce weight,improve lipid metabolism and insulin resistance,improve sex hormone disorder,and have a positive effect on pregnancy outcome.This review summarizes the impact of orlistat treatment on metabolism and fertility in obese women with PCOS.

关键词： hyperandrogenism insulin resistance obesity orlistat polycystic ovary syndrome pregnancy outcome

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Crossover patterns under meiotic chromosome program

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Asian Journal of Andrology 2021年第6期23卷 562-571页

作者： Shunxin Wang Yongliang Shang Yanlei Liu Binyuan Zhai Xiao Yang Liangran Zhang center for reproductive Medicine Cheeloo College of MedicineShandong 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 National research center for Assisted reproductive Technology and reproductive Genetics Shandong UniversityJinan 250012China Advanced Medical research Institute Shandong UniversityJinan 250014China State Key Laboratory of Microbial Technology Shandong UniversityQingdao 266237China

Repairing DNA double-strand breaks(DSBs)with homologous chromosomes as templates is the hallmark of meiosis.The critical outcome of meiotic homologous recombination is crossovers,which ensure faithful chromosome segregation and promote genetic diversity of progenies.Crossover patterns are tightly controlled and exhibit three characteristics:obligatory crossover,crossover interference,and crossover homeostasis.Aberrant crossover patterns are the leading cause of infertility,miscarriage,and congenital disease.Crossover recombination occurs in the context of meiotic chromosomes,and it is tightly integrated with and regulated by meiotic chromosome structure both locally and globally.Meiotic chromosomes are organized in a loop-axis architecture.Diverse evidence shows that chromosome axis length determines crossover frequency.Interestingly,short chromosomes show different crossover patterns compared to long chromosomes.A high frequency of human embryos are aneuploid,primarily derived from female meiosis errors.Dramatically increased aneuploidy in older women is the well-known“maternal age effect.”However,a high frequency of aneuploidy also occurs in young women,derived from crossover maturation inefficiency in human females.In addition,frequency of human aneuploidy also shows other age-dependent alterations.Here,current advances in the understanding of these issues are reviewed,regulation of crossover patterns by meiotic chromosomes are discussed,and issues that remain to be investigated are suggested.

关键词： aneuploidy chromosome crossover crossover interference crossover pattern meiosis recombination

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 system.The 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 documented.In 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 cells.Furthermore,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 follicles.Functionally,HFD enhanced follicle-stimulating hormone(FSH)sensitivity and hormone conversion,while OB caused decreased sensitivity,inadequate steroid hormone conversion,and impaired follicular development.These differences can be explained by the differential expression pattern of the transcription factor Foxo1.Overall,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

Comparison of the Developmental Potential and clinical Results of In Vivo Matured Oocytes Cryopreserved with Different Vitrification Media

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Chinese Medical Journal 2015年第22期128卷 3029-3034页

作者： Mei Li Miao-Miao Wang Hui Liu Ke-Liang Wu Shui-Ying Ma Cheng Li Hai-Bin Zhao Zi-Jiang Chen center for reproductive Medicine Provincial Hospital Affiliated to Shandong University National Research Center for Assisted Reproductive Technology andReproductive Genetics Key Laboratory for Reproductive Endocrinology of Ministry of EducatLon Shandong Provincial Key Laboratory of Reproductive Medicine Jinan Shandong 250021 China

Background： Oocyte vitrification is widely used throughout the world, but its clinical efficacy is inconsistent and depends on the vitrification media. This study compared the developmental potential and clinical results of in vivo matured oocytes cryopreserved with different vitrification media. Methods： This retrospective study involved vitrified-warmed oocytes at one in vitro fertilization laboratory. Vitrification media kits comprised the MC kit （ethylene glycol （EG] plus 1,2-propanediol [PROH]）, the KT kit （EG plus dimethyl sulphoxide [DMSO]）, and the Modified kit （EG plus DMSO and PROH kit）. Rates of oocyte survival and subsequent developmental potential were recorded and analyzed. The t-test and the Chi-square test were used to evaluate each method＇s efficacy. Results： Oocyte survival rate was significantly higher for the Modified kit （92.0%） than for the MC kit （88.2%）（P 〈 0.05） and the KT kit （77.3%）（P 〈 0.001）. The rate of high-quality embryo development in the Modified kit group （35.8%） was significantly higher than in the MC kit group （29.0%） and the KT kit group （28.3%）（P 〈 0.001 ）. No significant differences were observed in the clinical pregnancy and implantation rates among the MC, KT, and Modified kit groups （37.2% vs. 30.2% vs. 39.6%; 21.9% vs. 18.8% vs. 27.4%, respectively）（P 〉 0.05）. The high-quality embryo rate per warmed oocyte was significantly higher （23.4%） in the Modified kit group than in the other groups （P 〈 0.001）. The embryo utilization and live birth rates per warmed oocyte were the highest in the Modified kit group, but not significantly （P 〉 0.05）. Conclusions： Modified vitrification media are efficient for oocyte vitrification and. with further verification, may be able to replace commercially available media in future clinical applications.

关键词： Fertilization Live Birth Oocytes Pregnancy Vitrification Media

Roles of insulin-like growth factor Ⅱ in regulating female reproductive physiology

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Science China(Life Sciences) 2020年第6期63卷 849-865页

作者： Tahir Muhammad Mengjing Li Jianfeng Wang Tao Huang Shigang Zhao Han Zhao Hongbin Liu Zi-Jiang Chen center for reproductive Medicine Cheeloo College of MedicineShandong UniversityJinan 250012China National research center for Assisted reproductive Technology and reproductive Genetics Shandong UniversityJinan 250012China Key laboratory of reproductive Endocrinology of Ministry of Education Shandong UniversityJinan 250012China shandong provincial clinical Medicine research center for reproductive health Shandong UniversityJinan 250012China Shanghai Key Laboratory for Assisted Reproduction and reproductive Genetics Shanghai 20000China center for reproductive Medicine Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200000 China

The number of growth factors involved in female fertility has been extensively studied, but reluctance to add essential growth factors in culture media has limited progress in optimizing embryonic growth and implantation outcomes, a situation that has ultimately led to reduced pregnancy outcomes. Insulin-like growth factor Ⅱ(IGF-Ⅱ) is the most intricately regulated of all known reproduction-related growth factors characterized to date, and is perhaps the predominant growth factor in human ovarian follicles. This review aims to concisely summarize what is known about the role of IGF-Ⅱ in follicular development, oocyte maturation, embryonic development, implantation success, placentation, fetal growth, and in reducing placental cell apoptosis, as well as present strategies that use growth factors in culture systems to improve the developmental potential of oocytes and embryos in different species. Synthesizing the present knowledge about the physiological roles of IGF-Ⅱ in follicular development, oocyte maturation, and early embryonic development should, on the one hand, deepen our overall understanding of the potential beneficial effects of growth factors in female reproduction and on the other hand support development(optimization) of improved outcomes for assisted reproductive technologies.

关键词： growth factors IGF-Ⅱ oocyte maturation embryonic development placentation fetal growth

DENND1A desensitizes granulosa cells to FSH by arresting intracellular FSHR transportation

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Science China Life Sciences 2024年

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 reproductive Medicine center Guangdong Second Provincial General Hospital The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal Hospital Nanjing Medical University shandong Key Laboratory of reproductive Medicine Shandong University National research center for Assisted reproductive Technology and reproductive Genetics Shandong University Guangdong provincial People's Hospital Guangdong Academy of Medical Sciences State Key Laboratory of reproductive Medicine and Offspring health Jinan Gusu School Nanjing Medical University Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory Guangdong Second Provincial General Hospital Shanghai Key Laboratory for Assisted Reproduction and reproductive Genetics Key laboratory of reproductive Endocrinology of Ministry of Education Shandong University Institute of Women Children and Reproductive Health Shandong University center for reproductive Medicine Renji Hospital School of Medicine Shanghai Jiao Tong University research Unit of Gametogenesis and health of ART-Offspring Chinese Academy of Medical Sciences (No.2021RU001) Shandong Provincial Clinical Research Center for Reproductive Health

Polycystic ovary syndrome (PCOS) is a complex disorder. Genome-wide association studies (GWAS) have identified several genes associated with this condition, including DENND1A. DENND1A encodes a clathrin-binding protein that functions as a guanine nucleotide exchange factor involved in vesicular transport. However, the specific role of DENND1A in reproductive hormone abnormalities and follicle development disorders in PCOS remain poorly understood. In this study, we investigated DENND1A expression in ovarian granulosa cells (GCs)from PCOS patients and its correlation with hormones. Our results revealed an upregulation of DENND1A expression in GCs from PCOS cases, which was positively correlated with testosterone levels. To 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 stimulation. Additionally, the TG mice displayed diminished responsiveness to FSH, characterized by smaller ovary size, less well-developed follicles, and abnormal expressions of FSH-priming genes. Mechanistically, we found that Dennd1a overexpression disrupted the intracellular trafficking of follicle stimulating hormone receptor (FSHR), promoting its internalization and inhibiting recycling. These 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.

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