Endocrine Abstracts

JOINT2750

Background: Precocious puberty (PP) may lead to multiple adverse outcomes. Growing epidemiological evidence implicates that a high-fat diet (HFD) is closely related to precocious puberty (PP). Emerging evidence suggests that PP is a gut–brain axis disorder involving microbial-endocrine crosstalk. Hydroxytyrosol (HT) demonstrates multiple bioactive properties, yet its impact on PP remains unexplored. We aimed to investigate the effects of HT on PP and gut microbiota (GM) in animals.

Objective: This study aimed to explore the therapeutic potential of HT in HFD-induced PP through modulation of the gut microbiota (GM)-hypothalamic-pituitary-gonadal (HPG) axis.

Study design and methods: A PP model was established in feeding female Sprague-Dawley rats through HFD administrated from postnatal day 21, and with HT by gastric until virginal opening. Four experimental groups were evaluated: normal diet control (NC) group, HFD group, NC+HT group, and HFD+HT group. Puberty onset was monitored via vaginal opening timing. Blood, fecal, and hypothalamic samples were harvested to evaluate potential mechanistic pathways. Furthermore, fecal microbiota transplantation (FMT) was conducted to confirm the causality between HT and PP risk.

Results: Administration of HT in female offspring rats delayed vaginal opening and extended the first estrous cycle, accompanied by reduced serum estrogen, serum luteinizing hormone (LH) and follicle stimulating hormone (FSH). The 25 mg kg⁻¹ HT treatment significantly downregulated hypothalamic expression of gonadotropin-releasing hormone (GnRH) and kisspeptin proteins. These benefits were achieved through the modulation of the gut microbiome, which functionally suppressed the HPG axis and prevented PP progression. Notably, FMT experiments indicated that the causal correlation between HT intake and PP is mediated by the gut microbiome alterations.

Conclusion: Our findings establish HT as a novel microbiota-modulating agent that attenuates HFD-induced PP through gut microbiome-mediated regulation of neuroendocrine pathways. This suggests potential clinical applications of dietary polyphenols in PP prevention strategies.