摘要
正常的卵母细胞发育是成功受精和开启胚胎发育的保障,对于人类繁衍生育至关重要.卵母细胞发育是一个复杂而精细的过程,伴随着卵泡的生长和减数分裂的进行,受基因、遗传和环境等多种因素的调控.该过程起始于女性胎儿时期,先后经历原始生殖细胞和卵原细胞,随后进入减数分裂.卵母细胞在女性出生后就停滞在第一次减数分裂前期,青春期在激素的刺激下,恢复减数分裂,启动纺锤体组装,并完成纺锤体的双极化.随后,通过不对称分裂排出第一极体,并进入第二次减数分裂,很快停滞在第二次减数分裂中期,发育为成熟卵子.卵子受精后排出第二极体完成第二次减数分裂.其中任一过程出现异常都会导致卵母细胞发育缺陷和不孕.随着高分辨活细胞成像、辅助生殖和高通量测序等技术的发展,人们对人类卵母细胞发育有了新的认识,例如,发现人类卵母细胞微管组织中心、人独特的纺锤体双极化过程以及卵子发育异常新致病基因等.本文主要介绍人类卵母细胞发育过程、生理和病理机制、临床不孕患者遗传诊断及潜在干预策略.最后,对未来探索人类卵母细胞发育过程的生理和病理机制及临床干预策略进行了展望.
Normal oocyte development ensures successful fertilization and embryo development,playing a crucial role in human reproduction.This intricate process involves follicle growth and meiosis and is regulated by various factors,including genes,genetics,and environment.The development of oocytes begins during the female fetal stage.Oocytes undergo the stages of primordial germ cell and oogonium,and then enter meiosis.After birth,oocytes were arrested at the diplotene of prophase in meiosis I.Until puberty,under the stimulation of hormones,oocytes resume meiosis and develop into mature oocytes.Only mature oocytes can fuse with sperm for fertilization,and extrude the second polar body to complete meiosis.The maturation process of oocytes primarily consists of nuclear and cytoplasmic maturation.Nuclear maturation encompasses the arrest and resumption of meiosis,spindle assembly and migration,as well as polar body extrusion,etc.On the other hand,cytoplasmic maturation involves organelle reorganization,mRNA metabolism regulation,and protein homeostasis regulation,etc.With advancements in technologies such as high-resolution live cell imaging,assisted reproduction,and molecular biology,researchers have gained new insights into human oocyte development.For instance,they have discovered the microtubule organization center in human oocytes,the human-specific spindle bipolarization process,and the spindle stability mechanisms in human oocytes.Any abnormality in the process of oocyte development can lead to oocyte maturation defect,which further affects fertilization and embryonic development,ultimately resulting in female infertility.Previous studies have demonstrated that genetic variation,obesity,and aging are important factors influencing oocyte development.In recent years,with the advancements in high-throughput sequencing technology and genetics,more pathogenic genes responsible for human oocyte developmental defects have been reported.Currently,there are 37 known pathogenic genes,and patients carrying mutations in these genes exhibit a variety of clinical phenotypes,including oocyte maturation arrest,fertilization failure,and early embryonic arrest.These studies fully demonstrate that genetic factors are a significant cause of female infertility,and further emphasize the necessity of clinical genetic diagnosis.In clinical practice,the number of infertile patients suffering from repeated IVF/ICSI failures due to oocyte developmental defects is gradually increasing.Exploring effective intervention strategies is crucial for promoting reproductive health.Many studies have explored intervention strategies for oocyte developmental defects,including mitochondrial replacement therapy,antioxidant therapy,and small-molecule drug treatment.However,the feasibility and safety of these intervention strategies need to be further evaluated in human tissue and clinical studies.In addition,stem cell therapy has made a breakthrough in the field of reproductive medicine,exhibiting significant potential in improving women’s reproductive health.This technology has also brought new hope for the clinical treatment of infertility.This review introduces the developmental process of human oocytes,physiological and pathological mechanisms,genetic diagnosis for infertility patients,and potential intervention strategies.Finally,we provided a perspective on exploring the physiological and pathological mechanisms of human oocyte development,as well as clinical intervention strategies in the future.
作者
王伟杰
穆健
桑庆
王磊
Weijie Wang;Jian Mu;Qing Sang;Lei Wang(The International Peace Maternity and Child Health Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200030,China;Institutes of Biomedical Sciences,Fudan University,Shanghai 200032,China)
出处
《科学通报》
北大核心
2025年第15期2276-2301,共26页
Chinese Science Bulletin
基金
国家自然科学基金(82325021,82288102,32130029,82471885,82371663)
复旦曹娥江基础研究基金(24FCB01)资助。
关键词
卵母细胞发育
减数分裂
突变
女性不孕
辅助生殖
oocyte development
meiosis
mutation
female infertility
assisted reproduction
作者简介
王伟杰,同等贡献;穆健,同等贡献;联系人:王磊,E-mail:wangleiwanglei@fudan.edu.cn;联系人:桑庆,E-mail:sangqing@fudan.edu.cn。
