Effects of intracerebroventricular Metrnl administration on the hypothalamic-pituitary-testicular axis in male rats

Abstract

Background Metrnl (Meteorin-like) is a recently identified adipokine expressed in key components of the hypothalamic-pituitary-testicular (HPT) axis. However, its role in male reproductive function remains unclear. This study aimed to investigate the effects of central Metrnl administration on the HPT axis and spermatogenesis in male rats. Methods and results Forty adult male Wistar-Albino rats were randomly divided into four groups (n = 10 per group): control, sham, 10 nM Metrnl, and 100 nM Metrnl. Metrnl was administered via intracerebroventricular infusion for 14 days. Metrnl treatment significantly decreased hypothalamic GnRH mRNA and protein expression (p < 0.05). Accordingly, serum LH, FSH, and testosterone levels were significantly reduced in the treatment groups compared to controls (p < 0.05). Histological analysis revealed increased seminiferous tubule diameter and decreased germinal epithelial thickness (p < 0.05). Immunohistochemical evaluation demonstrated a dose-dependent reduction in HSD3B1 and vimentin immunoreactivity, more pronounced at 100 nM. Additionally, sperm concentration and motility were significantly decreased in both treatment groups (p < 0.05). Conclusions Central Metrnl administration suppresses the HPT axis at the hypothalamic level, leading to reduced gonadotropin and testosterone secretion. This suppression is associated with impaired Leydig and Sertoli cell function and diminished sperm quality. These findings identify Metrnl as a potential negative regulator of male reproductive function.