Akonom Tyler N, Allen Mary A, Tsai Pei-San
Department of Integrative Physiology, University of Colorado, Boulder, CO, United States.
Biofrontiers Institute, University of Colorado, Boulder, CO, United States.
Front Endocrinol (Lausanne). 2025 Apr 15;16:1571740. doi: 10.3389/fendo.2025.1571740. eCollection 2025.
Sexual interactions have previously been shown to improve reproductive health through unknown mechanisms. In this study, we used RNA-Seq to examine sex-induced gene expression changes in the preoptic area (POA), a critical reproductive brain region. Using a mouse model defective in fibroblast growth factor signaling (dnFGFR mouse), previously shown to disrupt the gonadotropin-releasing hormone (GnRH) system, we examined the impact of opposite sex (OS) housing on gene expression in the POA of a reproductively compromised animal. Bulk RNA-Seq followed by gene set enrichment analysis (GSEA) were used to analyze changes in gene expression and biological processes in control and dnFGFR mice after 300 days of cohabitation with a same sex or OS partner. OS housing of dnFGFR mice, but not control mice, significantly improved reproductive anatomy and gonadotropins in dnFGFR mice. These changes occurred concomitantly with novel biological processes related to estradiol metabolism and neuron excitation. Our results suggest a new role of neuron- or astrocyte-derived estradiol in the plasticity of the GnRH neuron population and offer a promising new direction for the treatment of reproductive disorders stemming from GnRH deficiency.
先前的研究表明，性互动可通过未知机制改善生殖健康。在本研究中，我们使用RNA测序技术来检测视前区（POA）——一个关键的生殖脑区——中性别诱导的基因表达变化。我们利用一种成纤维细胞生长因子信号传导缺陷的小鼠模型（dnFGFR小鼠），该模型先前已被证明会破坏促性腺激素释放激素（GnRH）系统，来研究异性同居对生殖功能受损动物POA中基因表达的影响。在与同性或异性伴侣同居300天后，我们使用批量RNA测序技术并结合基因集富集分析（GSEA）来分析对照小鼠和dnFGFR小鼠的基因表达及生物学过程的变化。dnFGFR小鼠而非对照小鼠的异性同居显著改善了dnFGFR小鼠的生殖解剖结构和促性腺激素水平。这些变化与雌二醇代谢和神经元兴奋相关的新生物学过程同时发生。我们的研究结果表明，神经元或星形胶质细胞衍生的雌二醇在GnRH神经元群体的可塑性中具有新作用，并为治疗由GnRH缺乏引起的生殖障碍提供了一个有前景的新方向。
