Beclin-1-dependent autophagy, but not apoptosis, is critical for stem-cell-mediated endometrial programming and the establishment of pregnancy.
Dev Cell
; 58(10): 885-897.e4, 2023 05 22.
Article
in En
| MEDLINE
| ID: mdl-37040770
ABSTRACT
The human endometrium shows a remarkable regenerative capacity that enables cyclical regeneration and remodeling throughout a woman's reproductive life. Although early postnatal uterine developmental cues direct this regeneration, the vital factors that govern early endometrial programming are largely unknown. We report that Beclin-1, an essential autophagy-associated protein, plays an integral role in uterine morphogenesis during the early postnatal period. We show that conditional depletion of Beclin-1 in the uterus triggers apoptosis and causes progressive loss of Lgr5+/Aldh1a1+ endometrial progenitor stem cells, with concomitant loss of Wnt signaling, which is crucial for stem cell renewal and epithelial gland development. Beclin-1 knockin (Becn1 KI) mice with disabled apoptosis exhibit normal uterine development. Importantly, the restoration of Beclin-1-driven autophagy, but not apoptosis, promotes normal uterine adenogenesis and morphogenesis. Together, the data suggest that Beclin-1-mediated autophagy acts as a molecular switch that governs the early uterine morphogenetic program by maintaining the endometrial progenitor stem cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Uterus
/
Endometrium
Limits:
Animals
/
Female
/
Humans
/
Pregnancy
Language:
En
Journal:
Dev Cell
Journal subject:
EMBRIOLOGIA
Year:
2023
Document type:
Article
Affiliation country:
Estados Unidos