Cinnamic Acid Ameliorates D-Galactose–Induced Premature Ovarian Failure in Mice and Alters Antioxidant and Angiogenesis-Related Gene Expression

Premature ovarian failure (POF) is characterized by ovarian dysfunction, infertility, and oxidative stress. Cinnamic acid (CA), a polyphenol with antioxidant properties, may protect ovarian function. This study evaluated the effects of CA in a D-galactose-induced mouse model of POF. Thirty NMRI mice were assigned to a control, a POF group, and three CA-treated groups (50, 100, and 200 mg/kg). POF was induced by daily D-galactose injection for 42 days, with CA co-administered during the last 14 days. Estrous cyclicity, ovarian histology, total antioxidant capacity (TAC), and mRNA expression of Nrf2, Foxo3a, Angpt1, Angpt2, and Vegfa were evaluated. D-gal disrupted estrous cycles, increased follicular atresia, and downregulated these genes. CA treatment improved estrous cyclicity, follicular development, and TAC, and increased gene expression relative to the POF group, with the most pronounced effects generally observed at 200 mg/kg. These findings suggest that CA may improve several features of D-galactose-induced ovarian dysfunction, potentially through enhanced antioxidant capacity. Changes in angiogenesis-related gene expression were inconsistent and should be considered exploratory rather than evidence of enhanced ovarian angiogenesis. Further protein-level, vascular, and functional studies are needed to clarify the biological significance and mechanisms of these effects.