ArticleScientific reports2025
Early-life macronutrient exposure alters pubertal timing through hypothalamic microRNA networks.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Early-Life High-Fat Diet Impairs Autophagy and Reduces GABANutrients · 2026Article
- Photoperiodic modulation of puberty through melatonin-kisspeptin-GnRH signalling in female Wistar rats.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2026Article
- Estradiol Reverses Ovariectomy-Induced Small RNA-mRNA Stress Signatures to Restore Neuroendocrine, Synaptic, and Immune Homeostasis in the Hypothalamus.Biomolecules · 2026Article
- Integrated omics approaches with non-thermal food fortification: pathways to personalized nutrition solutions.Frontiers in nutrition · 2026Review
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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