The autophagy protein, FIP200 (RB1CC1) mediates progesterone responses governing uterine receptivity and decidualization†

Arin K. Oestreich, Sangappa B. Chadchan, Alexandra Medvedeva, John P. Lydon, Emily S. Jungheim, Kelle H. Moley, Ramakrishna Kommagani

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)843-851
Number of pages9
JournalBiology of reproduction
Volume102
Issue number4
DOIs
StatePublished - Apr 15 2020
Externally publishedYes

Keywords

  • endometrium
  • fertility
  • hESCs
  • implantation
  • PR-Cre
  • pregnancy

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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