Parkin deficiency impairs female fertility, oocyte development, fertilization and mitochondrial function in mice

Parkin, a mitochondrial E3 ubiquitin ligase, plays a central role in mitophagy and cellular homeostasis. Although well studied in neurobiology, its role in female reproduction remains unclear. This study investigated the role of Parkin on female fertility using young (2-3 months old) and older (9-10 months old) mice with a global germline Parkin deletion. Parkin knockout (KO) females exhibited significantly reduced fertility with total pups per female lower in KO mice (16.0 ± 1.53) compared to wild type (WT) (22.33 ± 0.67; p = 0.02). In young mice, GV oocyte yield was significantly reduced in KO (30.0 ± 1.53) compared to WT (52.7 ± 6.96; p = 0.03), as was MII oocyte count (7.7 ± 0.67 vs. 22.3 ± 0.88; p = 0.0002). In older mice, similar trends were observed. Fertilization rates were significantly lower in KO mice compared to WT (36.2 ± 8.1% vs. 61.2 ± 5.5%; p = 0.03). RNA sequencing identified multiple differentially expressed genes between KO and WT, with associated pathway changes. These findings indicate that Parkin deficiency impairs oocyte yield, fertilization capacity, and overall fertility, suggesting that Parkin plays a key role in reproductive competence.