Partial rejuvenation of the spermatogonial stem cell niche after gender-affirming hormone therapy in trans women
Although the impact of gender-affirming hormone therapy (GAHT) on spermatogenesis in trans women has already been studied, data on its precise effects on the testicular environment is poor. Therefore, this study aimed to characterize, through histological and transcriptomic analysis, the spermatogon...
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eLife Sciences Publications Ltd
2025-01-01
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| author | Emily Delgouffe Samuel Madureira Silva Frédéric Chalmel Wilfried Cools Camille Raets Kelly Tilleman Guy T'Sjoen Yoni Baert Ellen Goossens |
| author_facet | Emily Delgouffe Samuel Madureira Silva Frédéric Chalmel Wilfried Cools Camille Raets Kelly Tilleman Guy T'Sjoen Yoni Baert Ellen Goossens |
| author_sort | Emily Delgouffe |
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| description | Although the impact of gender-affirming hormone therapy (GAHT) on spermatogenesis in trans women has already been studied, data on its precise effects on the testicular environment is poor. Therefore, this study aimed to characterize, through histological and transcriptomic analysis, the spermatogonial stem cell niche of 106 trans women who underwent standardized GAHT, comprising estrogens and cyproterone acetate. A partial dedifferentiation of Sertoli cells was observed, marked by the co-expression of androgen receptor and anti-Müllerian hormone which mirrors the situation in peripubertal boys. The Leydig cells also exhibited a distribution analogous to peripubertal tissue, accompanied by a reduced insulin-like factor 3 expression. Although most peritubular myoid cells expressed alpha-smooth muscle actin 2, the expression pattern was disturbed. Besides this, fibrosis was particularly evident in the tubular wall and the lumen was collapsing in most participants. A spermatogenic arrest was also observed in all participants. The transcriptomic profile of transgender tissue confirmed a loss of mature characteristics - a partial rejuvenation - of the spermatogonial stem cell niche and, in addition, detected inflammation processes occurring in the samples. The present study shows that GAHT changes the spermatogonial stem cell niche by partially rejuvenating the somatic cells and inducing fibrotic processes. These findings are important to further understand how estrogens and testosterone suppression affect the testis environment, and in the case of orchidectomized testes as medical waste material, their potential use in research. |
| format | Article |
| id | doaj-art-5179e04a3b524d73a813e156e170fba6 |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-5179e04a3b524d73a813e156e170fba62025-08-20T02:43:59ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.94825Partial rejuvenation of the spermatogonial stem cell niche after gender-affirming hormone therapy in trans womenEmily Delgouffe0https://orcid.org/0000-0001-5611-2173Samuel Madureira Silva1https://orcid.org/0000-0002-0833-123XFrédéric Chalmel2Wilfried Cools3Camille Raets4Kelly Tilleman5Guy T'Sjoen6Yoni Baert7Ellen Goossens8Biology of the Testis (BITE) Laboratory, Genetics, Reproduction and Development (GRAD) Research Group, Vrije Universiteit Brussel, Brussels, BelgiumBiology of the Testis (BITE) Laboratory, Genetics, Reproduction and Development (GRAD) Research Group, Vrije Universiteit Brussel, Brussels, BelgiumInserm, EHESP, Institut de Recherche en Santé, Environnement et Travail (IRSET), Université de Rennes, Rennes, FranceCore facility, Support for Quantitative and Qualitative Research (SQUARE), Vrije Universiteit Brussel, Brussels, BelgiumCore facility, Support for Quantitative and Qualitative Research (SQUARE), Vrije Universiteit Brussel, Brussels, BelgiumDepartment for Reproductive Medicine, Ghent University Hospital, Ghent, BelgiumDepartment of Endocrinology and Center for Sexology and Gender, Ghent University Hospital, Ghent, BelgiumBiology of the Testis (BITE) Laboratory, Genetics, Reproduction and Development (GRAD) Research Group, Vrije Universiteit Brussel, Brussels, Belgium; In Vitro Toxicology and Dermato-Cosmetology (IVTD), Vrije Universiteit Brussel, Brussels, BelgiumBiology of the Testis (BITE) Laboratory, Genetics, Reproduction and Development (GRAD) Research Group, Vrije Universiteit Brussel, Brussels, BelgiumAlthough the impact of gender-affirming hormone therapy (GAHT) on spermatogenesis in trans women has already been studied, data on its precise effects on the testicular environment is poor. Therefore, this study aimed to characterize, through histological and transcriptomic analysis, the spermatogonial stem cell niche of 106 trans women who underwent standardized GAHT, comprising estrogens and cyproterone acetate. A partial dedifferentiation of Sertoli cells was observed, marked by the co-expression of androgen receptor and anti-Müllerian hormone which mirrors the situation in peripubertal boys. The Leydig cells also exhibited a distribution analogous to peripubertal tissue, accompanied by a reduced insulin-like factor 3 expression. Although most peritubular myoid cells expressed alpha-smooth muscle actin 2, the expression pattern was disturbed. Besides this, fibrosis was particularly evident in the tubular wall and the lumen was collapsing in most participants. A spermatogenic arrest was also observed in all participants. The transcriptomic profile of transgender tissue confirmed a loss of mature characteristics - a partial rejuvenation - of the spermatogonial stem cell niche and, in addition, detected inflammation processes occurring in the samples. The present study shows that GAHT changes the spermatogonial stem cell niche by partially rejuvenating the somatic cells and inducing fibrotic processes. These findings are important to further understand how estrogens and testosterone suppression affect the testis environment, and in the case of orchidectomized testes as medical waste material, their potential use in research.https://elifesciences.org/articles/94825transgender womenspermatogonial stem cellstesticular tissuespermatogenesishormonal treatmentgerm cells |
| spellingShingle | Emily Delgouffe Samuel Madureira Silva Frédéric Chalmel Wilfried Cools Camille Raets Kelly Tilleman Guy T'Sjoen Yoni Baert Ellen Goossens Partial rejuvenation of the spermatogonial stem cell niche after gender-affirming hormone therapy in trans women eLife transgender women spermatogonial stem cells testicular tissue spermatogenesis hormonal treatment germ cells |
| title | Partial rejuvenation of the spermatogonial stem cell niche after gender-affirming hormone therapy in trans women |
| title_full | Partial rejuvenation of the spermatogonial stem cell niche after gender-affirming hormone therapy in trans women |
| title_fullStr | Partial rejuvenation of the spermatogonial stem cell niche after gender-affirming hormone therapy in trans women |
| title_full_unstemmed | Partial rejuvenation of the spermatogonial stem cell niche after gender-affirming hormone therapy in trans women |
| title_short | Partial rejuvenation of the spermatogonial stem cell niche after gender-affirming hormone therapy in trans women |
| title_sort | partial rejuvenation of the spermatogonial stem cell niche after gender affirming hormone therapy in trans women |
| topic | transgender women spermatogonial stem cells testicular tissue spermatogenesis hormonal treatment germ cells |
| url | https://elifesciences.org/articles/94825 |
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