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

HISTOCHEMISTRY AND CELL BIOLOGY, cilt.164, sa.94, ss.1-18, 2026 (Hakemli Dergi)

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 under-

stood. 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.