School of Basic Medical Science, Institute of Reproductive & Stem Cell Engineering, Central South University, Changsha, China.
School of Basic Medical Science, Center of Reproductive Health, Central South University, Changsha, China.
Biol Reprod. 2021 Jun 4;104(6):1262-1270. doi: 10.1093/biolre/ioab025.
The 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 ZP. 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 ZP, but ZP1 was detectable inside the cytoplasm. Only 1-2 eggs were recovered from oviducts of superovulated Zp1MT/MT females, while an average of 21 eggs were recovered from superovulated Zp1WT/WT per female. The eggs of Zp1MT/MT females were not surrounded by a ZP and lost their fertilization capacity in vitro. Zp1MT/MT females mated with wild-type males failed to become pregnant. Studies in 293T cells showed that mutant Zp1 resulted in a truncated ZP1 protein, which might be intracellularly sequestered and interacted 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.
透明带(ZP)在生殖过程中起着至关重要的作用,包括卵母细胞发生、受精和着床前发育。人和大鼠的 ZP 由四种糖蛋白组成,分别称为 ZP1、ZP2、ZP3 和 ZP4。我们之前的研究报道了人类不育症中一种新型的 Zp1 突变,与涉及 ZP 缺失的异常表型有关。在这里,我们开发了一种同源大鼠品系来研究其致病效应。纯合子(Zp1MT/MT)雌性的卵巢中既有生长中的卵母细胞,也有完全成熟的卵母细胞;这些卵母细胞完全没有透明带,但细胞质内可检测到 ZP1。超排卵的 Zp1MT/MT 雌性的输卵管中仅回收了 1-2 个卵子,而超排卵的 Zp1WT/WT 雌性平均每个卵巢中回收了 21 个卵子。Zp1MT/MT 雌性的卵子没有被 ZP 包裹,体外受精能力丧失。Zp1MT/MT 雌性与野生型雄性交配未能怀孕。在 293T 细胞中的研究表明,突变型 Zp1 导致 ZP1 蛋白截断,可能被细胞内隔离,并与野生型 ZP3 或 ZP4 相互作用。我们的结果表明,Zp1 点突变导致大鼠卵母细胞不孕和透明带缺失。