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

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
• endocytosis
• endometrium
• beclin-1
• stem cells
• morphogenesis

Acknowledgements

Our research was funded by grants from the National Institutes of Health/National Institute of Child Health and Human Development (grants R01HD102680, R01HD104813, and R01HD065435) to R.K.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Non-standard Abbreviations

BECN1- Beclin-1

Becn1 cKO- Beclin-1 conditional knockout

Becn1 KI- Beclin-1 Knock-in

PN- Postnatal

EPSCs- endometrial progenitor stem cells

FOXA-2- Forkhead box protein A2

BCL2- BCL2 apoptosis regulator

Aldh1a1-aldehyde dehydrogenase 1 family member A1

Lgr5 -leucine-rich repeat-containing G protein-coupled receptor 5

Additional information

Funding

The work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health