{"doi":"10.1101/2025.07.21.666020","title":"Functional Integration of Different-Sex Gonad Transplants into the Adult Mouse Hypothalamic Pituitary Gonadal Axis","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 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":570673,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1476564,"name":"Monica A. Rionda","orcid":null,"position":1,"is_corresponding":false},{"id":1287493,"name":"Evelyn Cho","orcid":"0000-0001-9992-7807","position":2,"is_corresponding":false},{"id":1476565,"name":"Jamison G. Clark","orcid":null,"position":3,"is_corresponding":false},{"id":1288022,"name":"R Krüger","orcid":null,"position":4,"is_corresponding":false},{"id":1287492,"name":"Ruth K. Chan‐Sui","orcid":"0009-0000-9619-7116","position":5,"is_corresponding":false},{"id":232456,"name":"Vasantha Padmanabhan","orcid":"0000-0002-8443-7212","position":6,"is_corresponding":false},{"id":237464,"name":"Molly B. Moravek","orcid":"0000-0001-9972-4938","position":7,"is_corresponding":false},{"id":237466,"name":"Ariella Shikanov","orcid":"0000-0003-0159-6419","position":8,"is_corresponding":false},{"id":895890,"name":"Daniel R. Pfau","orcid":"0000-0002-4510-647X","position":0,"is_corresponding":true}],"reference_count":112,"raw_metadata":null,"created_at":"2026-07-19T02:57:11.713851Z","pmid":"40777414","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}