Background There is a tendency for early onset of puberty in children and adolescents worldwidely. And excessive consumption of unhealthy diets such as sugary drinks may be a contributing factor.

Objective To investigate the effects of cola and diet cola exposure on the initiation of puberty in male mice.

Methods Female C57BL/6J mice were exposed to cola and diet cola starting from the day when vaginal plugs were detected, with the exposure continuing until the onset of puberty indicators in male offspring. During this period, male offspring were regularly weighed, and their daily water intake and food consumption were monitored. On the day when puberty onset indicators were observed, mice were euthanized, and serum, testicular, and hypothalamic tissues were collected to analyze hormone levels and measure the expression of key genes regulating puberty initiation.

Results Compared with the control group, mice in the cola group and the diet cola group had a significant increase in body weight, an increase in water intake, and a decrease in food intake, and both the increase in water intake and the decrease in food intake of mice in the diet cola group were lower than those in the cola group, the differences were statistically significant (all P < 0.05). Compared with the control group, the time of penile peeling was significantly earlier in the cola group (P < 0.01) and the diet cola group (P < 0.01). The testicular organ coefficient was significantly higher (P < 0.01), and spermatogenic tubule epithelial thickness was significantly increased (P < 0.01) in the cola group, while there was no significant difference in testicular organ coefficient (P > 0.05), and spermatogenic tubule epithelial thickness was significantly increased (P < 0.05) in the diet cola group. Sera hormone levels of GnRH (P < 0.05), LH (P < 0.05), and FSH (P < 0.01) were significantly higher in the cola and diet cola groups compared to the control group. For mechanisms, mRNA expression levels of HPG axis-related genes TTF-1, KISS-1, GPR54, and GnRH were significantly upregulated in the hypothalamic tissues of mice in the cola group and the diet cola group (P < 0.05), and the mRNA expression levels of energy metabolism-related genes POMC were significantly downregulated (P < 0.01). In testicular tissues, Cyp1b1 mRNA expression was significantly decreased (P < 0.05), whereas no significant changes were observed for Cyp19a1 (P > 0.05).

Conclusion Early-life exposure to cola and diet cola may promote precocious puberty onset in male mice by modulating the upstream HPG axis gene TTF-1, thereby influencing the expression of KISS-1, GPR54, and GnRH genes within the HPG axis. This process enhances the secretion of hormones such as GnRH, LH, and FSH, subsequently regulating the expression of the Cyp1b1 gene in the testes.