Chronic stress disturbs neuroendocrine control of reproduction and fertility in male rats

Currently, stress is considered one of the risk factors for infertility in male humans, altering sperm function. Sperm production and maturation depends on the hypothalamic-pituitary-testis axis control. Therefore, the objective of the current study was to evaluate the effects of chronic stress on the neuroendocrine control of male reproduction, the oxidative status in the epididymis, and male fertility. Adult male rats were assigned to control or chronic stress groups. Chronically stressed males were exposed to cold-water immersion (CWI) for 50 consecutive days. After euthanasia, the hypothalamus was dissected for Kisspeptin (Kiss1) and Gonadotropin releasing hormone (GnRH) evaluation; serum luteinizing hormone (LH), testosterone (T), and corticosterone concentrations were determined. In the epididymis, reactive oxygen species (ROS), lipid peroxides, and content of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx4) were assessed. Sperm motility, viability, concentration, morphology and acrosomal reaction were assessed. Epididymal sperm were used for in-vitro fertilization with oocytes from intact female rats. Stressed males showed lower hypothalamic Kiss1 and GnRH content, lower LH and T concentration, together with higher serum corticosterone concentration. ROS production, and lipid peroxides increased in all epididymal regions, while SOD, CAT, and GPx4 content decreased after chronic stress; sperm quality was also lower. The percentage of fertilized oocytes decreased, and embryonic development was low, compared to controls. Together, these results show that chronic stress disrupts neuroendocrine control of male reproduction and generates oxidative stress in the epididymis. These effects disturb sperm quality, leading to low fertilizing potential and poor embryonic development.