Neuroinflammatory-mediated dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis following perioperative stress in male rats: A mechanistic investigation

Abstract

Perioperative stress can disrupt neuroendocrine function, but the contribution of neuroinflammatory signaling to hypothalamic-pituitary-gonadal (HPG) axis suppression remains incompletely defined. This study examined the association between perioperative stress, hypothalamic inflammatory markers and HPG-axis hormones in adult male Wistar rats. A controlled experimental design was used in 180 rats randomly assigned to control, sham-operated and laparotomy groups. Blood and hypothalamic tissue were collected postoperatively. IL-1β, IL-6, TNF-α, corticosterone, GnRH, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone were measured by ELISA. Data were analyzed using one-way ANOVA with Tukey post-hoc testing and multiple linear regression. Laparotomy significantly increased hypothalamic IL-1β, IL-6, TNF-α and corticosterone and reduced GnRH, LH, FSH and testosterone. The regression model explained 81.2% of the variance in testosterone, with IL-1β, IL-6 and TNF-α showing significant negative standardized associations after adjustment for corticosterone. These findings support an association between perioperative inflammatory signaling and HPG-axis suppression, but they do not establish causal mediation. Further studies using formal mediation designs and mechanistic interventions are warranted.