Autophagy is required for stem-cell-mediated endometrial programming and the establishment of pregnancy

Autophagy. 2024 Apr;20(4):970-972. doi: 10.1080/15548627.2023.2231270. Epub 2023 Jul 5.

Abstract

Autophagy plays an important role in the normal growth and morphogenesis of a variety of tissues. Its role in uterine maturation, however, is not fully characterized. Recently, we reported that BECN1 (Beclin1)-dependent autophagy, but not apoptosis, is crucial for stem cell-mediated endometrial programming and the establishment of pregnancy in mice. Upon genetic and pharmacological inhibition of BECN1-mediated autophagy, female mice displayed severe endometrial structural and functional defects leading to infertility. Specifically, conditional loss of Becn1 in the uterus induces apoptosis and results in the gradual loss of endometrial progenitor stem cells. Importantly, the restoration of BECN1-driven autophagy, but not apoptosis in Becn1 conditionally ablated mice promoted normal uterine adenogenesis and morphogenesis. Overall, our findings emphasize the critical role of intrinsic autophagy in endometrial homeostasis and on the molecular underpinnings of uterine differentiation.

Keywords: Autophagy; apoptosis; beclin-1; endocytosis; endometrium; morphogenesis; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy* / physiology
  • Beclin-1 / metabolism
  • Endometrium* / metabolism
  • Female
  • Mice
  • Pregnancy
  • Stem Cells* / cytology
  • Stem Cells* / metabolism
  • Uterus

Substances

  • Beclin-1