Successful establishment of pregnancy depends on steroid hormone-driven cellular changes in the uterus during the peri-implantation period. To become receptive to embryo implantation, uterine endometrial stromal cells (ESCs) must transdifferentiate into decidual cells that secrete factors necessary for embryo survival and trophoblast invasion. Autophagy is a key homeostatic process vital for cellular homeostasis. Although the uterus undergoes major cellular changes during early pregnancy, the precise role of autophagy in uterine function is unknown. Here, we report that conditional knockout of the autophagy protein FIP200 in the reproductive tract of female mice results in reduced fecundity due to an implantation defect. In the absence of FIP200, aberrant progesterone signaling results in sustained uterine epithelial proliferation and failure of stromal cells to decidualize. Additionally, loss of FIP200 impairs decidualization of human ESCs. We conclude that the autophagy protein FIP200 plays a crucial role in uterine receptivity, decidualization, and fertility. These data establish autophagy as a major cellular pathway required for uterine receptivity and decidualization in both mice and human ESCs.

中文翻译：

---

自噬蛋白 FIP200 (RB1CC1) 介导控制子宫容受性和蜕膜化的孕酮反应†

妊娠的成功建立取决于在着床期间子宫内类固醇激素驱动的细胞变化。为了接受胚胎植入，子宫内膜基质细胞 (ESC) 必须转分化为蜕膜细胞，分泌胚胎存活和滋养细胞侵袭所需的因子。自噬是对细胞稳态至关重要的关键稳态过程。尽管子宫在怀孕早期经历了重大的细胞变化，但自噬在子宫功能中的确切作用尚不清楚。在这里，我们报告了雌性小鼠生殖道中自噬蛋白 FIP200 的条件性敲除会导致由于着床缺陷导致的生育力降低。在没有 FIP200 的情况下，异常的孕酮信号导致持续的子宫上皮增殖和基质细胞蜕膜失败。此外，FIP200 的缺失会损害人类 ESC 的蜕膜化。我们得出结论，自噬蛋白 FIP200 在子宫容受性、蜕膜化和生育能力中起着至关重要的作用。这些数据将自噬确立为小鼠和人类 ESC 中子宫容受性和蜕膜化所需的主要细胞途径。