摘要
男性不育是一类多因素的复杂疾病.作为导致男性不育的重要因素,弱畸精子症越来越受到人们的关注并且被发现与遗传因素有关.随着高通量测序技术的不断发展,多个弱畸精子症的致病基因被揭示.其中,对于在人和小鼠中进化保守的致病基因,利用传统的基因编辑小鼠模型即可完成表型或致病机理的探究.然而,随着研究的进行,人们陆续发现了与生殖疾病相关的一类灵长类特异基因(primate specific genes, PSGs),即存在人类基因组中、在灵长类和小鼠进化分支产生后出现的基因.对于此类基因,小鼠不再是疾病研究的理想模型,新的动物模型以及研究系统的探索尤为必要.本文在总结前期利用小鼠模型开展弱畸精子症遗传致病机理以及干预探究的基础上,重点介绍了新近发现的灵长类特异基因在男性生殖系统中的作用及研究系统构建.相关论述不仅为遗传咨询和临床诊断提供理论指导,也将为睾丸组织中富集的灵长类特异基因在生殖系统中的功能探索提供新的研究思路.
Male infertility is a complex and multifactorial condition,attracting growing attention due to its significant impact on reproductive health.One crucial aspect contributing to male infertility is asthenoteratozoospermia,which has been increasingly linked to genetic factors.With the advent of advanced high-throughput sequencing technology,researchers have unveiled a plethora of genes associated with asthenoteratozoospermia.Traditionally,standard gene-edited mice have served as valuable models for investigating the phenotypes and underlying pathogenic mechanisms of genes that are evolutionarily conserved between humans and mice.These early studies utilizing mice are foundational and important for contemporary perspectives.However,as our understanding of this important condition deepens,scientists have identified a subset of primate-specific genes(PSGs)that play a pivotal role in reproductive-related diseases.PSGs are genes unique to the human genome and have emerged following the evolutionary divergence of primates and mice.Consequently,mice no longer represent the ideal models for studying diseases involving PSGs,necessitating the exploration of novel animal models and research systems.In this comprehensive review,we consolidate the body of research conducted with mouse models to elucidate the genetic underpinnings of asthenoteratozoospermia and interventions.We also shift our focus to the recent revelations regarding the significant role of PSGs within the male reproductive system.Moreover,we delve into the development of research frameworks tailored to studying PSGs.This review not only offers a foundation for genetic counseling and clinical diagnosis but also ignites fresh research concepts for unraveling the functions of primate-specific genes,which are notably enriched in the male reproductive system.This represents a stepping stone toward a more complete understanding of male infertility and the development of effective treatment strategies moving forward.
作者
周大鹏
李阔阔
田世雄
周怡伶
张锋
贺小进
刘春雨
ZHOU DaPeng;LI KuoKuo;TIAN ShiXiong;ZHOU YiLing;ZHANG Feng;HE XiaoJin;LIU ChunYu(Obstetrics and Gynecology Hospital,State Key Laboratory of Genetic Engineering,Institute of Reproduction and Development,Fudan University,Shanghai 2000ll,China;Human Phenome Institute,Institute of Metabolism and Integrative Biology,Fudan University,Shanghai 200438,China;The First Affiliated Hospital of Anhui Medical University,NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract,Anhui MedicalUniversity,Hefei230022,China;International Peace Maternity and Child Health Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200030,China)
出处
《中国科学：生命科学》
CSCD
北大核心
2024年第1期94-102,共9页
Scientia Sinica(Vitae)
