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

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.

Automated summary

Autophagy plays a crucial role in the normal growth and morphogenesis of various tissues, including the uterus. Our study reveals that BECN1-dependent autophagy is essential for stem cell-mediated endometrial programming and the establishment of pregnancy in mice. Inhibition of BECN1-mediated autophagy leads to severe endometrial defects and infertility, highlighting the critical role of autophagy in maintaining endometrial homeostasis and uterine differentiation.