High-yielding dairy cows often experience metabolic stress during early lactation, leading to subclinical ketosis (SCK) and reproductive impairment. This study investigates how SCK-associated conditions (hypoglycemia and elevated nonesterified fatty acids, NEFA) affect bovine granulosa cell (GC) function via the PI3K/AKT pathway. Primary GCs were cultured under four metabolic conditions for 24 h: normal glucose (NG), low glucose (LG), NG + high NEFA, and LG + high NEFA. Additional groups treated with the PI3K/AKT activator SC79 or inhibitor LY294002 under LG + NEFA stress were included. Combined LG + NEFA stress reduced cell viability, increased apoptosis, impaired steroidogenesis, and disrupted mitochondrial function. While LG alone increased p-AKT, NEFA alone suppressed this. SC79 rescued these effects, whereas LY294002 exacerbated them. These findings demonstrate that metabolic stressors disrupt GC proliferation, steroidogenesis, and mitochondrial homeostasis through PI3K/AKT pathway dysregulation, offering insights into the SCK-associated reproductive dysfunction.
Bu et al. (Wed,) studied this question.