Opposite sex housing enhances reproductive function and induces transcriptional changes in the preoptic area of GnRH-deficient mice

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...

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Main Authors: Tyler N. Akonom, Mary A. Allen, Pei-San Tsai
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1571740/full
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author Tyler N. Akonom
Mary A. Allen
Pei-San Tsai
author_facet Tyler N. Akonom
Mary A. Allen
Pei-San Tsai
author_sort Tyler N. Akonom
collection DOAJ
description 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.
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spelling doaj-art-0098b54abfee488da182a48d2c1ee8142025-08-20T03:08:31ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-04-011610.3389/fendo.2025.15717401571740Opposite sex housing enhances reproductive function and induces transcriptional changes in the preoptic area of GnRH-deficient miceTyler N. Akonom0Mary A. Allen1Pei-San Tsai2Department of Integrative Physiology, University of Colorado, Boulder, CO, United StatesBiofrontiers Institute, University of Colorado, Boulder, CO, United StatesDepartment of Integrative Physiology, University of Colorado, Boulder, CO, United StatesSexual 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.https://www.frontiersin.org/articles/10.3389/fendo.2025.1571740/fullgonadotropin-releasing hormone neuronsfibroblast growth factor receptorpreoptic areahypothalamic-pituitary-gonadal axissexual interactionsreproduction
spellingShingle Tyler N. Akonom
Mary A. Allen
Pei-San Tsai
Opposite sex housing enhances reproductive function and induces transcriptional changes in the preoptic area of GnRH-deficient mice
Frontiers in Endocrinology
gonadotropin-releasing hormone neurons
fibroblast growth factor receptor
preoptic area
hypothalamic-pituitary-gonadal axis
sexual interactions
reproduction
title Opposite sex housing enhances reproductive function and induces transcriptional changes in the preoptic area of GnRH-deficient mice
title_full Opposite sex housing enhances reproductive function and induces transcriptional changes in the preoptic area of GnRH-deficient mice
title_fullStr Opposite sex housing enhances reproductive function and induces transcriptional changes in the preoptic area of GnRH-deficient mice
title_full_unstemmed Opposite sex housing enhances reproductive function and induces transcriptional changes in the preoptic area of GnRH-deficient mice
title_short Opposite sex housing enhances reproductive function and induces transcriptional changes in the preoptic area of GnRH-deficient mice
title_sort opposite sex housing enhances reproductive function and induces transcriptional changes in the preoptic area of gnrh deficient mice
topic gonadotropin-releasing hormone neurons
fibroblast growth factor receptor
preoptic area
hypothalamic-pituitary-gonadal axis
sexual interactions
reproduction
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1571740/full
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AT peisantsai oppositesexhousingenhancesreproductivefunctionandinducestranscriptionalchangesinthepreopticareaofgnrhdeficientmice