Retinoblastoma protein promotes uterine epithelial cell cycle arrest and necroptosis for embryo invasion.

ABSTRACT: Retinoblastoma protein (RB) encoded by Rb1 is a prominent inducer of cell cycle arrest (CCA). The hormone progesterone (P₄ ) promotes CCA in the uterine epithelium and previous studies indicated that P₄ activates RB by reducing the phosphorylated, inactive form of RB. Here, we show that embryo implantation is impaired in uterine-specific Rb1 knockout mice. We observe persistent cell proliferation of the Rb1-deficient uterine epithelium until embryo attachment, loss of epithelial necroptosis, and trophoblast phagocytosis, which correlates with subsequent embryo invasion failure, indicating that Rb1-induced CCA and necroptosis of uterine epithelium are involved in embryo invasion. Pre-implantation P₄ supplementation is sufficient to restore these defects and

SUBMITTER: Akaeda S 

PROVIDER: S-EPMC7857437 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature