Wang Fang, Li Shijie, Meng Lingshuai, Kuang Ye, Liu Zhonghua, Ma Xinghong
College of Life Science, Northeast Agricultural University, No. 600 Changjiang Street, Xiangfang District, Harbin, 150030, China.
Departments of Gynecology and Obstetrics, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
Reprod Sci. 2022 Oct;29(10):2864-2875. doi: 10.1007/s43032-022-00902-5. Epub 2022 Mar 7.
Implantation timing is critical for a successful pregnancy. A short delay in embryo implantation caused by targeted gene ablation produced a cascading problem in the later stages of the pregnancy. Although several delayed implantation models have been established in wild mice, almost none of them is suitable for investigating the early delay's effects on the late events of pregnancy. Here, we report a new delayed implantation model established by the intraperitoneal administration of letrozole at 5 mg/kg body weight on day 3 of pregnancy. In these mice, initiation of implantation was induced at will by the injection of estradiol (E2). When the estradiol (3 ng) was injected on day 4 of pregnancy (i.e., without delay), the embryo implantation restarted, and the pregnancy continued normally. However, 25 ng estrogen caused compromised implantation. We also found that 67% of the female mice could be pregnant normally and finally gave birth when the estradiol injection (3 ng) was on day 5 of pregnancy (i.e., 1-day delay). Most failed pregnancies had impaired decidualization, decreased serum progesterone levels, and compromised angiogenesis. Progesterone supplementation could rescue decidualization failure in the mice. Collectively, we established a new model of delayed implantation by letrozole, which can be easily applied to study the effect and mechanisms of delay of embryo implantation on the progression of late pregnancy events.
着床时机对于成功怀孕至关重要。靶向基因消融导致的胚胎着床短暂延迟在妊娠后期引发了一系列问题。尽管在野生小鼠中已经建立了几种延迟着床模型，但几乎没有一种适用于研究早期延迟对妊娠后期事件的影响。在此，我们报告一种新的延迟着床模型，该模型通过在妊娠第3天腹腔注射5 mg/kg体重的来曲唑建立。在这些小鼠中，通过注射雌二醇（E2）可随意诱导着床启动。当在妊娠第4天（即无延迟）注射雌二醇（3 ng）时，胚胎着床重新开始，妊娠正常继续。然而，25 ng雌激素会导致着床受损。我们还发现，当在妊娠第5天（即延迟1天）注射雌二醇（3 ng）时，67%的雌性小鼠能够正常怀孕并最终分娩。大多数妊娠失败的小鼠蜕膜化受损、血清孕酮水平降低且血管生成受损。补充孕酮可挽救小鼠的蜕膜化失败。总的来说，我们通过来曲唑建立了一种新的延迟着床模型，该模型可轻松应用于研究胚胎着床延迟对妊娠后期事件进展的影响及机制。
