Mutant Zp1 impedes incorporation of ZP3 and ZP4 in the zona pellucida, resulting in zona absence and female infertility in rats
| Autor: | Hang-Jing Tan, Hong-Mei Xiao, Da-Jing Yi, Chao Lv, Hong-Wen Deng, Tian-Liu Peng, Hua-Lin Huang, Ru-Ping Quan |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Infertility Mutant Biology Zona Pellucida Glycoproteins Oogenesis Andrology 03 medical and health sciences 0302 clinical medicine Human fertilization Homologous chromosome medicine Animals Zona pellucida Zona Pellucida 030219 obstetrics & reproductive medicine Ovary Female infertility Cell Biology General Medicine medicine.disease Oocyte Rats 030104 developmental biology medicine.anatomical_structure Reproductive Medicine Female Infertility Female |
| Zdroj: | Biology of Reproduction. 104:1262-1270 |
| ISSN: | 1529-7268 0006-3363 |
| DOI: | 10.1093/biolre/ioab025 |
| Popis: | 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.Summary sentenceZp1 mutation can lead to congenital deficiencies and ZP loss, which leads to human infertility. The interaction between truncated ZP1 and ZP3 or ZP4 is gained, which affects their normal transport and secretion, suggesting that normal ZP1 is crucial for the structure of the ZP and for fertility. |
| Databáze: | OpenAIRE |
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