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

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ABSTRACTGender‐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.