{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T06:15:58Z","timestamp":1788156958203,"version":"build-2803163510"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>During puberty, secondary sexual characteristics develop alongside processes of testicular cell differentiation and maturation. Puberty suppression has been introduced to prevent the development of these physical changes in some individuals who request it, as is the case with gender dysphoria. However, not everyone continues with the treatment. Therefore, the objective of this study was to determine the testicular changes caused by the temporary suppression of puberty, initiated at different stages of development, in an experimental model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>A total of 56 male rats were used, distributed equally into four study groups. A Control group, which received saline, and three experimental groups that received the GnRH analog (GnRHa), leuprolide acetate at 25\u00a0\u03bcg\/kg\/day. In the first of these groups, administration of the analog began during early puberty (LeuEP) on day postpartum (dpp) 25, equivalent to Tanner stages II-III in humans; in the second group, administration began during advanced puberty (LeuAP) at 35 dpp, equivalent to Tanner stages IV-V; and in the postpubertal group (LeuPP), administration began at 60 dpp. Half of the number of animals in each group were euthanized at 90 dpp, while the remaining animals had the GnRHa removed to allow recovery and were euthanized at 190 dpp. Testicular tissue was collected to assess histological and ultrastructural changes, as well as proteins that regulate the functional activity of Sertoli and Leydig cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The LeuEP and LeuAP groups exhibited seminiferous tubules atrophy with peritubular cell hyperplasia, resulting in thickened tubular walls. They also showed Leydig cell hyperplasia with low immunoreactivity to the HSD17B3 enzyme, reduced immunoreactivity to androgen receptor proteins, and vimentin disorganization. These same groups showed partial recovery at 190 dpp, without reaching the values of the Control group. This may have been due to the persistence of thick tubular walls, possibly resulting from the dysfunction of Leydig cells and peritubular cells, which impeded the paracrine action of molecules necessary to maintain spermatogenesis. Furthermore, this was compounded by Sertoli cell dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Therefore, the temporary arrest of puberty initiated during puberty resulted in permanent testicular alterations, unlike in animals where GnRHa administration began postpubertally.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1936689","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:41:35Z","timestamp":1788154895000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-term testicular changes caused by the temporary suspension of puberty initiated at different stages of development"],"prefix":"10.3389","volume":"14","author":[{"given":"Christian","family":"Mancilla-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Maestr\u00eda en Biolog\u00eda de la Reproducci\u00f3n Animal, Universidad Aut\u00f3noma Metropolitana, Unidad Iztapalapa","place":["Ciudad de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itzel Jatziri","family":"Contreras-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda de la Reproducci\u00f3n, Instituto Nacional de Pediatr\u00eda","place":["Ciudad de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio C\u00e9sar","family":"Rojas-Casta\u00f1eda","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda de la Reproducci\u00f3n, Instituto Nacional de Pediatr\u00eda","place":["Ciudad de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Adrian","family":"Landero-Huerta","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda de la Reproducci\u00f3n, Instituto Nacional de Pediatr\u00eda","place":["Ciudad de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Reynoso-Robles","sequence":"additional","affiliation":[{"name":"Laboratorio de Morfolog\u00eda Celular y Tisular, Instituto Nacional de Pediatr\u00eda","place":["Ciudad de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Osvaldo","family":"Cuevas-Alpuche","sequence":"additional","affiliation":[{"name":"Servicio de Urolog\u00eda, Instituto Nacional de Pediatr\u00eda","place":["Ciudad de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Mar\u00eda","family":"Vigueras-Villase\u00f1or","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda de la Reproducci\u00f3n, Instituto Nacional de Pediatr\u00eda","place":["Ciudad de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1111\/iep.12261","article-title":"Correlation between testicular mast cell count and spermatogenic epithelium in non-obstructive azoospermia","volume":"99","author":"Abdel-Hamid","year":"2018","journal-title":"Int. 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