# Functional Integration of Different‐Sex Gonad Transplants Into the Adult Mouse Hypothalamic Pituitary Gonadal Axis

## TL;DR

This study explores how different-sex gonad transplants can function in adult mice, potentially offering new insights for gender-affirming hormone therapy.

## Contribution

The study introduces a novel pre-clinical model using different-sex gonad transplants to explore gender-affirming hormone therapy.

## Key findings

- Gonadectomized mice with different-sex gonad transplants show steroidogenesis and gametogenesis.
- Pituitary and hypothalamic mRNA expression patterns depend on the transplanted gonad's sex.
- Transplanted gonads function independently of the host's sex, suggesting HPG axis plasticity.

## Abstract

Gender‐affirming hormone therapy (GAHT) relies on exogenous hormones to produce hormonal milieus that achieve and/or maintain embodiment goals. Another potential route to these endpoints is transplantation of novel steroidogenic tissue. To develop a pre‐clinical model, we asked whether different‐sex gonad transplants can be functionally integrated into the adult mouse hypothalamic‐pituitary‐gonadal (HPG) axis. Adult male and female mice are gonadectomized and implanted with gonads from genetically matched but different‐sex pups. Controls received gonads from same‐sex pups. Temporal changes to gonadotropin and steroid hormone levels reveal the decoupling of the HPG following gonadectomy and gonad‐dependent levels after transplanting donor gonads. After six weeks, histological structures in transplanted gonads are consistent with expected steroidogenesis and gametogenesis. Interestingly, pituitary, ARC, and AVPV mRNA showed gonad‐ and sex‐dependent expression patterns. Future work with this technique could lead to translation to gender affirming care and explorations of gonad‐dependent sex differences in biomedical and basic research.

This study introduces and investigates different‐sex gonad transplants in a mouse model of gender‐affirming hormone therapy. Ovaries and testes implanted into gonadectomized adults exhibit gametogenesis and steroidogenesis independent of the sex of the host. Gonad‐dependent neurotransmitter and steroid hormone receptor mRNA expression in the hypothalamus and pituitary may facilitate this surprising plasticity in adulthood.