Mitochondria as integrative regulators of ferroptosis in the female reproductive system.

Mitochondrial function is fundamental to female reproductive physiology, supporting follicular development, oocyte maturation, and endometrial remodeling. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently emerged as a potential contributor to reproductive dysfunction under conditions of mitochondrial impairment and oxidative stress. This review examines how mitochondrial quality-control (MQC) mechanisms-including biogenesis, dynamics, iron handling, and redox regulation-modulate ferroptotic sensitivity across female reproductive tissues. We highlight cell-type-specific differences, ranging from ferroptosis-associated granulosa cell loss during follicular atresia to sublethal ferroptotic stress affecting oocyte competence and tightly restrained ferroptosis during decidualization and implantation. By integrating experimental and clinical evidence, we propose that mitochondrial regulation of ferroptosis acts as a context-dependent modulator of reproductive function rather than a uniform cell death pathway. Understanding this interplay provides new insight into ovarian aging, infertility, and uterine receptivity, with implications for reproductive medicine.