State Key Laboratory of Reproductive Medicine, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing, China.
Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
PeerJ. 2022 May 3;10:e13370. doi: 10.7717/peerj.13370. eCollection 2022.
It has been thought that oocyte may develop in a low oxygen environment, as changes in follicle structure and formation of a fluid-filled antrum. The survival of hypoxic tissues is controlled by hypoxia-inducible factors (HIFs) that are activated in a low oxygen state. HIF1 is expressed in mature mouse oocytes and continues to be expressed after fertilization, from the 2-cell to blastocyst stage. However, the physiological roles of HIF pathway during oogenesis and embryogenesis have still not been elucidated in detail.
Mutant mice with oocyte-specific HIF1 deletion were generated by crossing 1 mice with transgenic mice expressing -promoter-mediated Cre recombinase. Breeding assay was carried out to detect female fertility. fertilization and embryo culture were used to assess early embryo development. Oocyte meiotic progression was also examined. Quantitative RT-PCR was used for analyzing of candidate genes expression.
We successfully generated mutant mice with oocyte-specific deletion of HIF1. Oocytes loss of HIF1 did not affect female fertility, ovulation and early embryo development. Moreover, oocytes can mature in vitro, and form well-organized spindle in the absence of HIF1. In addition, pronounced differences in and mRNA expression were not observed in HIF1-deleted oocytes. These results revealed that HIF pathway in oocytes is not essential for female fertility.
人们认为卵母细胞可能在低氧环境中发育,因为卵泡结构发生变化并形成充满液体的腔。缺氧组织的存活受缺氧诱导因子 (HIF) 控制,在低氧状态下激活。HIF1 在成熟的小鼠卵母细胞中表达,并在受精后继续表达,从 2 细胞期到囊胚期。然而,HIF 途径在卵发生和胚胎发生中的生理作用尚未详细阐明。
通过将 1 小鼠与表达 -启动子介导的 Cre 重组酶的转基因小鼠杂交,产生卵母细胞特异性 HIF1 缺失的突变小鼠。进行繁殖试验以检测雌性生育能力。体外受精和胚胎培养用于评估早期胚胎发育。还检查了卵母细胞减数分裂进程。使用定量 RT-PCR 分析候选基因的表达。
我们成功地产生了卵母细胞特异性 HIF1 缺失的突变小鼠。HIF1 缺失的卵母细胞不影响雌性生育能力、排卵和早期胚胎发育。此外,在没有 HIF1 的情况下,卵母细胞可以体外成熟,并形成组织良好的纺锤体。此外,在 HIF1 缺失的卵母细胞中未观察到 和 mRNA 表达的明显差异。这些结果表明卵母细胞中的 HIF 途径对于雌性生育能力不是必需的。