Mutant Zp1 impedes incorporation of ZP3 and ZP4 in the zona pellucida, resulting in zona absence and female infertility in rats

Biol Reprod. 2021 Feb 24:ioab025. doi: 10.1093/biolre/ioab025. Online ahead of print.ABSTRACTThe zona pellucida (ZP) plays vital roles in reproductive processes including oogenesis, fertilization and preimplantation development. Both human and rat ZP consist of four glycoproteins, called ZP1, ZP2, ZP3 and ZP4. Our previous research reported a novel Zp1 mutation in cases of human infertility, associated with an abnormal phenotype involving the absence of the zona pellucida. Here, we developed a homologous rat strain to investigate the pathogenic effect. The ovaries of homozygous (Zp1MT/MT) females possessed both growing and fully grown oocytes; the oocytes completely lacked a zona pellucida, but ZP1 was detectable inside the cytoplasm. Only 1-2 eggs were recovered from oviducts of superovulated Zp1MT/MT females, while ≈ 21 eggs were recovered from superovulated Zp1WT/WT females. The eggs of Zp1MT/MT females were not surrounded by a zona pellucida and lost their fertilization capacity in vitro. Zp1MT/MT females mated with wild-type males failed to become pregnant. Studies in 293 T cells showed that mutant Zp1 resulted in a truncated ZP1 protein, which might be intracellularly sequestered and interact with wild-type ZP3 or ZP4. Our results suggest that the Zp1 point mutation led to infertility and loss of the ZP in oocytes in rats.PMID:33624742 | DOI:10.1093/biolre/ioab025
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Source Type: research