The sperm quality in DIO male mice is linked to the NF-κB signaling and Ppp2ca expression in the hypothalamus.

Recent studies show obesity correlated with reduced sperm quality in males, but the mechanism is unclear. In this study, diet-induced obese (DIO) male mice exhibited disrupted luteinizing hormone (LH) pulse release due to altered function of the hypothalamic-pituitary-gonadal (HPG) axis. This alteration was caused by activation of nuclear factor kappa B (NF-κB) signaling in the hypothalamus, which led to decreased sperm quality. RNA sequencing (RNA-seq) analysis of the hypothalamic arcuate nucleus (ARC) revealed a signaling network involving protein phosphatase 2 catalytic subunit alpha (Ppp2ca). This network disrupted LH pulse secretion by inhibiting Akt kinase (AKT) and cAMP responsive element-binding protein 1 (CREB1) activities, thereby reducing KiSS-1 metastasis-suppressor (Kiss1) expression. Furthermore, overexpression of the Ppp2ca gene in the ARC led to disrupted LH patterns and reduced sperm quality. These findings offer new insights into the molecular mechanisms underlying sperm quality decline in DIO male mice.