Genetic mechanisms of infertility due to fertilization deficiency
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 PLCζ and 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 PLCζ test 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.
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