Hilz Emily N, Streifer Madeline, Milewski Tyler M, Gore Andrea C
Division of Pharmacology & Toxicology, The University of Texas at Austin, Austin, TX, 78712, USA; Center for Molecular Carcinogenesis & Toxicology, The University of Texas at Austin, Austin, TX, 78712, USA.
Division of Pharmacology & Toxicology, The University of Texas at Austin, Austin, TX, 78712, USA; Center for Molecular Carcinogenesis & Toxicology, The University of Texas at Austin, Austin, TX, 78712, USA.
Mol Cell Endocrinol. 2025 Oct 1;608:112616. doi: 10.1016/j.mce.2025.112616. Epub 2025 Jul 19.
The hypothalamic arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV) are critical regulators of reproductive function, energy balance, stress, and neuromodulation. These regions undergo substantial changes in neural and glial populations over development that enable the acquisition of adult functions. Although previous studies have examined developmental changes in specific hypothalamic cell populations or gene families, to our knowledge, none has comprehensively compared unbiased/bulk transcriptional profiles across key developmental stages in both the ARC and AVPV. In this study, we used 3' targeted RNA sequencing to profile gene expression in the ARC and AVPV of female rats at infantile (P8), peripubertal (P30), and adult (P60) life stages. We conducted unbiased and a priori selected differential gene expression analyses, the latter genes selected for their roles in reproduction, metabolism, stress, and neuromodulation. We also measured serum hormones as an index of physiology. Developmental analyses revealed robust differential gene expression between the infantile and prepubertal periods in both the ARC and AVPV, with substantial transcriptional overlap between regions. Fewer and more region-specific transcriptional changes were observed during the transition to adulthood. Gene ontology (GO) analyses revealed coordinated developmental programming prior to puberty, including downregulation of developmental processes and upregulation of metabolic and regulatory pathways. In adulthood, the AVPV showed continued transcriptional remodeling, while the ARC remained comparatively stable. FSH emerged as the strongest hormonal correlate of a priori hypothalamic gene expression. These data provide a reference for understanding hypothalamic development and hormone-gene interactions across life stages in the female rat.
下丘脑弓状核（ARC）和室周前腹侧核（AVPV）是生殖功能、能量平衡、应激和神经调节的关键调节因子。在发育过程中，这些区域的神经和胶质细胞群会发生显著变化，从而实现成年功能的获得。尽管先前的研究已经考察了特定下丘脑细胞群或基因家族的发育变化，但据我们所知，尚无研究全面比较ARC和AVPV在关键发育阶段的无偏倚/整体转录谱。在本研究中，我们使用3'靶向RNA测序来分析雌性大鼠在幼年（P8）、青春期前后（P30）和成年（P60）生命阶段ARC和AVPV中的基因表达。我们进行了无偏倚和先验选择的差异基因表达分析，后者选择的基因在生殖、代谢、应激和神经调节中发挥作用。我们还测量了血清激素作为生理指标。发育分析显示，ARC和AVPV在婴儿期和青春期前之间存在强烈的差异基因表达，区域间存在大量转录重叠。在向成年期过渡期间，观察到的区域特异性转录变化较少且更多。基因本体（GO）分析揭示了青春期前的协调发育编程，包括发育过程的下调以及代谢和调节途径的上调。在成年期，AVPV显示出持续的转录重塑，而ARC则相对稳定。促卵泡生成素（FSH）成为先验下丘脑基因表达的最强激素关联物。这些数据为理解雌性大鼠生命各阶段下丘脑发育和激素-基因相互作用提供了参考。
