Soyasaponin Aa prevents obesity-related precocious puberty by inhibiting hypothalamic-pituitary-gonadal axis in female Sprague-Dawley rats

Objective: Early-onset puberty is a major reason for pediatric Endocrinology clinics, particularly among girls. Obesity is linked to disruptions in the hypothalamic-pituitary-gonadal (HPG) axis, thereby leading to early-onset puberty. This study was designed to investigate the regulatory effects of soyasaponin Aa in an animal model of obesity-associated precocious puberty.

Study design: A rat model of obesity-induced precocious puberty was established through high-fat diet (HFD) feeding, which closely mimics the condition in children caused by excessive caloric intake. Obesity was assessed through body weight, serum lipid levels, and gonadal fat mass. Western blotting was performed to assess key adipogenesis regulators (PPARγ and C/EBPα) in gonadal white adipose tissues. ELISA was used to analyze serum levels of Hormones (LH, FSH, and GnRH). The mRNA expression of HPG axis-related genes in the hypothalamus, pituitary gland, and ovary were detected by RT-qPCR. Histopathological changes in ovarian and uterine tissues were examined using hematoxylin and eosin staining.

Results: Soyasaponin Aa significantly reduced body weight gain in HFD-fed rats and suppressed increases in serum lipid levels and gonadal white adipose tissue mass. It inhibited HFD-induced lipogenesis, as indicated by reduced expression of PPARγ and C/EBPα. Soyasaponin Aa effectively delayed puberty onset in female rats, as evidenced by prolonged vaginal opening and first estrous cycle, reduced endometrium thickness, and lower uterine and ovarian weights, along with suppressed follicular maturation. The HFD group showed elevated serum LH and FSH levels and increased hypothalamic GnRH secretion, all of which were significantly counteracted by soyasaponin Aa. Moreover, soyasaponin Aa downregulated HPG axis-related gene expression.

Conclusion: Soyasaponin Aa protects against obesity-induced precocious puberty by suppressing the activation of HPG axis.