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

## TL;DR

Cadmium exposure in male rats disrupts puberty by altering key genes in the neuroendocrine system and reducing testosterone levels.

## Contribution

This study reveals how cadmium affects the Kisspeptin–GnRH axis and delays puberty in male rats.

## Key findings

- Cadmium exposure reduced serum testosterone levels and total antioxidant capacity.
- Cd delayed pubertal onset and decreased hypothalamic Kiss1, Kiss1r, and Gnrh1 gene expression.
- These changes suggest cadmium acts as an endocrine disruptor affecting male reproductive maturity.

## Abstract

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 Kiss1, Kiss1r, and Gnrh1 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 Kiss1 expression, whereas at PND 49, it reduced Kiss1r and Gnrh1 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.