Abstract
In patients with polycystic ovary syndrome (PCOS), the concentration of homocysteine (Hcy) in follicular fluid is inversely correlated with oocyte and embryo quality. Nevertheless, other metabolic abnormalities associated with PCOS may also impact oocyte and early embryo quality. Therefore, it remains uncertain whether reproductive function is affected in patients without PCOS with hyperhomocysteinemia (HHcy). Here, we observed reduced fertility, increased ovarian atretic follicles, and reduced oocyte maturation rates in HHcy mice. Proteomic analyses revealed that HHcy causes mitochondrial dysfunction and reduced expression of zona pellucida proteins (ZP1, ZP2, and ZP3) in oocytes. Transmission electron microscopy confirmed abnormal formation of the zona pellucida and microvilli in oocytes from HHcy mice. Additionally, in vitro fertilization (IVF) demonstrated a reduction in the rate of 2-cell embryo formation in HHcy mice. These findings reveal that HHcy reduces female reproductive longevity by affecting follicular development and oocyte quality.