Scholarlink

<p>Pubertal timing is modulated by early-life nutrition through epigenetic mechanisms that remain incompletely understood. This study investigated how macronutrient-specific diets influence hypothalamic microRNA (miRNA) expression and pubertal onset in female Wistar rats. Animals were exposed to High-Fat (HFD), High-Carbohydrate (HCD), High-Protein (HPD), and Cafeteria diets (CafD) from postnatal day 21–42 followed with comprehensive analysis of phenotypic markers, hormone levels, ovarian histology, in-silico structural modelling and hypothalamic microRNA (miRNA) transcriptomics. Energy-dense diets (HFD, HCD) significantly advanced vaginal opening by 4–5 days compared to controls and increased body weight, serum Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), and Estradiol levels compared to control. Small RNA sequencing revealed extensive miRNA reprogramming, with over 490 differentially expressed miRNAs in each dietary group. Key findings included upregulation of miR-30b (targeting <i>Mkrn3</i>, a pubertal inhibitor), downregulation of miR-199 (targeting <i>Kiss1</i>, a pubertal activator), and altered expression of let-7 family miRNAs affecting developmental timing genes. Quantitative PCR validation confirmed inverse relationships between regulatory miRNAs and their target mRNAs involved in HPG axis control. In-silico structural modelling supported the thermodynamic stability of predicted miRNA-mRNA interactions. Functional enrichment analysis revealed convergence on GnRH signalling, MAPK pathways, and neuroendocrine regulation. These findings suggest that early nutritional environments may influence hypothalamic miRNA networks, potentially contributing to long-term neuroendocrine modulation.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Early-life macronutrient exposure alters pubertal timing through hypothalamic microRNA networks

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月19日

查看全文
  • Harsh Shah,
  • Sripriya Bulusu,
  • Hetvi Shah,
  • Nehareeka Dan,
  • Ankita Salunke,
  • A. V. Ramachandran,
  • Parth Pandya

摘要

Pubertal timing is modulated by early-life nutrition through epigenetic mechanisms that remain incompletely understood. This study investigated how macronutrient-specific diets influence hypothalamic microRNA (miRNA) expression and pubertal onset in female Wistar rats. Animals were exposed to High-Fat (HFD), High-Carbohydrate (HCD), High-Protein (HPD), and Cafeteria diets (CafD) from postnatal day 21–42 followed with comprehensive analysis of phenotypic markers, hormone levels, ovarian histology, in-silico structural modelling and hypothalamic microRNA (miRNA) transcriptomics. Energy-dense diets (HFD, HCD) significantly advanced vaginal opening by 4–5 days compared to controls and increased body weight, serum Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), and Estradiol levels compared to control. Small RNA sequencing revealed extensive miRNA reprogramming, with over 490 differentially expressed miRNAs in each dietary group. Key findings included upregulation of miR-30b (targeting Mkrn3, a pubertal inhibitor), downregulation of miR-199 (targeting Kiss1, a pubertal activator), and altered expression of let-7 family miRNAs affecting developmental timing genes. Quantitative PCR validation confirmed inverse relationships between regulatory miRNAs and their target mRNAs involved in HPG axis control. In-silico structural modelling supported the thermodynamic stability of predicted miRNA-mRNA interactions. Functional enrichment analysis revealed convergence on GnRH signalling, MAPK pathways, and neuroendocrine regulation. These findings suggest that early nutritional environments may influence hypothalamic miRNA networks, potentially contributing to long-term neuroendocrine modulation.