受精障碍导致人类不孕不育的遗传机制

Genetic mechanisms of infertility due to fertilization deficiency

受精是一个复杂的过程,超活化的精子和卵母细胞相互识别、融合,精子激活卵母细胞后形成原核,最后发育成受精卵.授精后卵母细胞内无原核形成或原核数异常,则称为受精障碍.受精障碍是由精子和/或卵母细胞的缺陷所导致的.调控精子超活化的CATSPER家族基因突变,精子顶体反应相关基因ACR和KCNU1突变,卵母细胞透明带相关基因ZP2突变均会造成精卵识别/融合障碍.精子中影响PLCζ及其定位的相关基因突变(PLCZ1,DPY19L2,SPATA16,PICK1,SPACA1,ZPBP1,CSNK2A2,CCDC62,ACTL9,ACTL7A,IQCN)导致卵母细胞激活障碍.卵母细胞中皮质反应相关基因ASTL突变,卵母细胞特异性酪氨酸激酶编码基因WEE2突变,RNA结合蛋白编码基因PATL2突变,皮质下母源复合物相关基因突变(TLE6,NLRP2,NLRP5),减数分裂双链DNA断裂形成基因REC114突变,纺锤体组装相关基因TUBB8,CDC20突变导致原核形成障碍.利用精子参数检测、形态检测、顶体酶活检测、卵母细胞激活试验及精子PLCζ检测等对受精障碍患者的检测可对其进行亚型分类,有助于制定相应的诊疗方案,实现该类患者的精准诊疗.

Fertilization is a complex process,in which hyperactivated sperm and oocyte recognize and fuse with each other.After the sperm activates the oocyte,pronuclei are formed and eventually develops into a zygote.If there is no formation of the pronuclei or have an abnormal number of pronuclei in the oocyte after insemination,it is called fertilization deficiency.Infertility is caused by defects in sperm and/or oocyte.Mutations in CATSPER family genes that regulating sperm hyperactivation,mutations in ACR and KCNU1 related to acrosomal reaction in sperm,and ZP2 related to zona pellucida in oocyte lead to sperm-egg recognition/fusion deficiency.Mutations in sperm related to PLCζand its localization(PLCZ1,DPY19L2,SPATA16,PICK1,SPACA1,ZPBP1,CSNK2A2,CCDC62,ACTL9,ACTL7A and IQCN)lead to oocyte activation deficiency.In oocyte,mutations in cortical reaction related gene ASTL,the oocyte-specific tyrosine kinase encoding gene WEE2,the RNA-binding protein encoding gene PATL2,and the subcortical maternal complex related genes(TLE6,NLRP2 and NLRP5),as well as mutations in the meiotic DNA double-stranded break formation gene REC114 and spindle related genes TUBB8 and CDC20,can lead to pronuclei formation deficiency.The use of semen parameters and morphology analyses,sperm acrosin activity test,oocyte activation test and sperm PLCζtest for the detection of patients with fertilization deficiency can be used to classify them into subtypes,which helps to develop corresponding diagnosis and treatment plans and achieve precise diagnosis and treatment for these patients.