Cadmium-Induced Neuroendocrine Alterations: Gene Expression of the Kisspeptin–GnRH Axis and Delayed Puberty in Male Rats

Puberty is a neuroendocrine process required for sexual maturity; it is regulated by the hypothalamic-hypophysis-gonadal (HHG) axis. Kisspeptin (KISS1) plays a vital role in activating this axis by stimulating the secretion of gonadotropin-releasing hormone (GnRH). Cadmium (Cd) exposure disrupts KISS1 signaling in female rodents; its effects on hypothalamic gene expression during male puberty remain poorly understood. This study investigated the effects of Cd exposure on hypothalamic <i>Kiss1</i>, <i>Kiss1r</i>, and <i>Gnrh1</i> expression, preputial separation (PS) as a marker of pubertal onset, testosterone levels, Cd concentration, and total antioxidant capacity (TAC) in the serum and hypothalamus of pubertal male Wistar rats. Animals received once a week intraperitoneal injection of CdCl₂ (1 mg/Kg body weight/100 µL) or saline (100 µL) and were euthanized on postnatal day (PND) 35 or 49. Cd exposure reduced serum testosterone levels and TAC. Also, pubertal onset was delayed. At PND 35, Cd decreased hypothalamic <i>Kiss1</i> expression, whereas at PND 49, it reduced <i>Kiss1r</i> and <i>Gnrh1</i> expression. These results suggest that Cd alters hypothalamic gene expression, which may contribute to delayed puberty and impaired sexual maturity. Our findings suggest the vulnerability of puberty to exposure to Cd, acting as an endocrine disruptor and neurotoxicant, with alterations for male reproductive maturity.