Department of Pediatrics, Traditional Chinese Medicine Hospital of Zhuji, Zhuji, Zhejiang, China.
Department of Clinical Lab, Traditional Chinese Medicine Hospital of Zhuji, Zhuji, Zhejiang, China.
Front Endocrinol (Lausanne). 2024 Feb 29;15:1285666. doi: 10.3389/fendo.2024.1285666. eCollection 2024.
Precocious puberty (PP) is a prevalent endocrine disorder affecting the physical and mental wellbeing of children. Identifying the triggering factors of PP has become a central issue. This study seeks to investigate the metabolomic and transcriptomic alterations in PP.
First, 37 school-aged girls diagnosed with PP and 25 age-matched prepubertal control girls were recruited, and the fecal samples were collected for non-targeted metabolomic analysis to screen for differentially expressed metabolites (DEMs). Subsequently, an animal model of PP was constructed by danazol administration to neonatal female rats, and both fecal non-targeted metabolomics and serum next-generation transcriptomic sequencing were performed to screen DEMs and differentially expressed genes (DEGs) in PP. Moreover, the DEM co-existing in clinical and animal models was administrated to PP rats to explore the role of the target metabolite in PP.
A total of 24 DEMs in PP clinical samples and 180 DEMs and 425 DEGs in PP animal samples were identified. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEMs and DEGs were enriched in disease-associated pathways, including fatty acid synthesis, glycerolipid metabolism, pyrimidine metabolism, steroid hormone biosynthesis, progesterone-mediated oocyte maturation, and gonadotropin-releasing hormone (GnRH) signaling pathway, forming a tight DEM-DEG pathway regulatory network. Further DEM validation demonstrated that thymine supplementation delayed the opening of the vagina and development of PP in model rats.
This study reveals that the metabolomic and transcriptomic changes, along with enriched pathways, are implicated in PP based on clinical and animal analyses. The findings may provide new strategies and research avenues for PP treatment.
性早熟（PP）是一种常见的内分泌紊乱疾病，影响儿童的身心健康。确定 PP 的触发因素已成为一个核心问题。本研究旨在探讨 PP 中的代谢组学和转录组学变化。
首先，招募了 37 名被诊断为 PP 的学龄期女孩和 25 名年龄匹配的青春期前对照组女孩，并采集粪便样本进行非靶向代谢组学分析，以筛选差异表达代谢物（DEMs）。随后，通过给予丹那唑给新生雌性大鼠构建 PP 动物模型，同时进行粪便非靶向代谢组学和血清下一代转录组测序，以筛选 PP 中的 DEMs 和差异表达基因（DEGs）。此外，将临床和动物模型中共同存在的 DEM 施用于 PP 大鼠，以探讨目标代谢物在 PP 中的作用。
在 PP 临床样本中鉴定出 24 个 DEM，在 PP 动物样本中鉴定出 180 个 DEM 和 425 个 DEG。京都基因与基因组百科全书（KEGG）通路分析表明，这些 DEM 和 DEG 富集在与疾病相关的通路中，包括脂肪酸合成、甘油脂质代谢、嘧啶代谢、类固醇激素生物合成、孕激素介导的卵母细胞成熟和促性腺激素释放激素（GnRH）信号通路，形成一个紧密的 DEM-DEG 通路调节网络。进一步的 DEM 验证表明，胸腺嘧啶补充延迟了模型大鼠阴道开口和 PP 的发育。
本研究通过临床和动物分析表明，代谢组学和转录组学变化以及富集的途径与 PP 有关。这些发现可能为 PP 的治疗提供新的策略和研究途径。
