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

## TL;DR

Exposure to the opposite sex improves reproductive function in mice with a genetic defect, possibly through changes in brain gene activity related to estradiol and neurons.

## Contribution

The study identifies novel estradiol-related processes and neuronal plasticity in GnRH-deficient mice due to opposite sex housing.

## Key findings

- OS housing improved reproductive anatomy and gonadotropins in dnFGFR mice.
- Transcriptional changes in the POA were linked to estradiol metabolism and neuron excitation.
- Findings suggest a new role for neuron- or astrocyte-derived estradiol in GnRH neuron plasticity.

## Abstract

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.