Hormonal regulation of mitochondrial dynamics- and mitophagy-related marker expression in the endometrium and placenta.

Abstract

Mitochondrial dynamics and mitophagy are indispensable for cellular homeostasis in hormonally regulated tissues such as the endometrium and placenta. Decidualization of endometrial stromal cells (ESCs) into decidual cells (DCs) requires extensive mitochondrial remodeling, yet how ovarian steroids regulate this process in vivo and in vitro remains incompletely understood. This study elucidates the modulation of mitochondrial fusion, fission, and mitophagy by estrogen (E2) and progesterone (P4) across the menstrual cycle and during pregnancy. Endometrial tissues were collected from women at early (EP) and late (LP) proliferative, and early (ES), mid (MS), and late (LS) secretory phases, while placental tissues were obtained from first-trimester (FP) and term pregnancies (TP). The expression of MFN2 and OPA1 (fusion), Drp1, Fis1, and MFF (fission), and Pink1 and Parkin (mitophagy) was assessed by immunohistochemistry in vivo. In vitro, the effects of E2 and P4 on these markers were examined in ESCs and DCs using western blotting. Mitochondrial morphology was evaluated by transmission electron microscopy and morphometry. In vivo, FP-DCs exhibited increased expression of fission- and mitophagy-related proteins, while in vitro P4 treatment was associated with increased Drp1 expression in FP-DCs. Collectively, these findings suggest that mitochondrial dynamics- and mitophagy-related protein changes accompany ESC-to-DC differentiation, with P4-associated Drp1 regulation potentially contributing to early pregnancy adaptation. Understanding these processes may provide insight into mechanisms relevant to implantation failure and pregnancy loss.