Functional Integration of Different-Sex Gonad Transplants into the Adult Mouse Hypothalamic Pituitary Gonadal Axis

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 were 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 were 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.