
ATG14 is critical for maintaining the structural integrity and cellular plasticity of the oviduct, preventing unscheduled pyroptosis activation, and enabling the timely transport of embryos from the oviduct to the uterus for successful implantation.


coremsg

Recurrent pregnancy loss (RPL), characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition to embryo quality and endometrial function, proper oviduct function is also essential for successful pregnancy establishment. Therefore, structural abnormalities or inflammation resulting from infection in the oviduct may impede the transport of embryos to the endometrium, thereby increasing the risk of miscarriage. However, the precise cellular mechanisms that maintain the structural and functional integrity of the oviduct are not studied yet. Here, we report that autophagy is critical for maintaining the oviduct homeostasis and keeping the inflammation under check to enable embryo transport. Specifically, the loss of the autophagy-related gene, Atg14 in the oviduct causes severe structural abnormalities compromising its cellular plasticity and integrity leading to the retention of embryos. Interestingly, the selective loss of Atg14 in oviduct ciliary epithelial cells did not impact female fertility, highlighting the specificity of ATG14 function in distinct cell types within the oviduct. Mechanistically, loss of Atg14 triggered unscheduled pyroptosis leading to inappropriate embryo retention and impeded embryo transport in the oviduct. Finally, pharmacological activation of pyroptosis in pregnant mice led to an impairment in embryo transport. Together, we found that ATG14 safeguards against unscheduled pyroptosis activation to enable embryo transport from the oviduct to uterus for the successful implantation. Of clinical significance, these findings provide possible insights on the underlying mechanism(s) of early pregnancy loss and might aid in developing novel prevention strategies using autophagy modulators.

### Competing Interest Statement

The authors have declared no competing interest.

*   WT
    :   Wild Type
    HESCs
    :   Human Endometrial stromal cells
    dpc
    :   Days post coitum
    E2
    :   Estrogen
    P4
    :   Progesterone
    cKO
    :   conditional knockout

The autophagy protein, ATG14 safeguards against unscheduled pyroptosis activation to enable embryo transport during early pregnancy

autophagy-protein-atg14-safeguards-oviduct-function-to-enable-embryo-transport-during-early-pregnancy


Autophagy Protein ATG14 Safeguards Oviduct Function to Enable Embryo Transport During Early Pregnancy
