{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T13:26:33Z","timestamp":1781875593321,"version":"3.54.5"},"reference-count":72,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Studies of adult depressed patients report that selective serotonin (5-HT) reuptake inhibitors (SSRIs) like clomipramine (CMI) have secondary effects on sperm quality. The epididymis possesses an autonomous serotonergic system critical for sperm maturation, whose establishment during neonatal development remains unexplored as a target for SSRI programming. We hypothesized that neonatal CMI exposure would disrupt the developing epididymal 5-HT system, leading to permanent sperm dysfunction. CMI (30 mg\/kg s.c.) was administered to male rats between postnatal days 8\u201321. At 3 months, sperm from the epididymal cauda was evaluated, and 5-HT levels were measured in the testis, caput, and cauda epididymis. Our novel findings demonstrate that neonatal CMI exposure induces region-specific, long-term alterations in epididymal 5-HT levels (decreased in caput, increased in cauda) without affecting testicular 5-HT. This reprogramming of the local serotonergic milieu was associated with reduced sperm concentration, viability, normal morphology, and motility, alongside increased mitochondrial activity and reactive oxygen species. This study reveals, for the first time, that the epididymal serotonergic system is a key target for neonatal SSRI programming, providing a mechanistic link (altered 5-HT homeostasis) between early-life exposure and persistent sperm defects in adulthood.<\/jats:p>","DOI":"10.3390\/ijms27031535","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T12:51:56Z","timestamp":1770209516000},"page":"1535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neonatal Clomipramine Exposure Disrupts Epididymal Serotonin Signaling and Programs Sperm Dysfunction in Adult Rats"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7505-0809","authenticated-orcid":false,"given":"Herlinda","family":"Bonilla-Jaime","sequence":"first","affiliation":[{"name":"Laboratorio de Psicobiol\u00f3gia Conductual, Departamento de Biolog\u00eda de la Reproducci\u00f3n, Universidad Aut\u00f3noma Metropolitana-Iztapalapa, Mexico City 09340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3688-5598","authenticated-orcid":false,"given":"Ofelia","family":"Lim\u00f3n-Morales","sequence":"additional","affiliation":[{"name":"Laboratorio de Psicobiol\u00f3gia Conductual, Departamento de Biolog\u00eda de la Reproducci\u00f3n, Universidad Aut\u00f3noma Metropolitana-Iztapalapa, Mexico City 09340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4426-0587","authenticated-orcid":false,"given":"Ernesto","family":"Rodr\u00edguez-Tob\u00f3n","sequence":"additional","affiliation":[{"name":"Laboratorio de Morfofisiolog\u00eda y Bioqu\u00edmica del Espermatozoide, Departamento de Biolog\u00eda de la Reproducci\u00f3n, Universidad Aut\u00f3noma Metropolitana-Iztapalapa, Mexico City 09340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3194-1175","authenticated-orcid":false,"given":"Jos\u00e9 Edwin","family":"Mendoza-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Doctorado en Biolog\u00eda Experimental, Divisi\u00f3n de Ciencias Biologicas y de la Salud, Universidad Aut\u00f3noma Metropolitana-Iztapalapa, Mexico City 09340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5756-150X","authenticated-orcid":false,"given":"David Yoab","family":"Jaimes","sequence":"additional","affiliation":[{"name":"Maestr\u00eda en Biolog\u00eda de la Reproducci\u00f3n Animal, Divisi\u00f3n de Ciencias Biologicas y de la Salud, Universidad Aut\u00f3noma Metropolitana-Iztapalapa, Mexico City 09340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9410-8535","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Cort\u00e9s-Altamirano","sequence":"additional","affiliation":[{"name":"Departamento de Neurociencias, Instituto Nacional de Rehabilitaci\u00f3n, \u201cLuis Guillermo Ibarra Ibarra\u201d, Calzada M\u00e9xico Xochimilco No. 289 Col., Arenal de Guadalupe, Mexico City 14389, Mexico"},{"name":"Departamento de Quiropr\u00e1ctica, Universidad Estatal del Valle de Ecatepec, Ecatepec de Morelos 55210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4599-1253","authenticated-orcid":false,"given":"Alfonso","family":"Alfaro-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Departamento de Neurociencias, Instituto Nacional de Rehabilitaci\u00f3n, \u201cLuis Guillermo Ibarra Ibarra\u201d, Calzada M\u00e9xico Xochimilco No. 289 Col., Arenal de Guadalupe, Mexico City 14389, 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Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6067-6868","authenticated-orcid":false,"given":"Lenin","family":"Pav\u00f3n","sequence":"additional","affiliation":[{"name":"Laboratorio de Psicoinmunolog\u00eda, Direcci\u00f3n de Investigaciones en Neurociencias del Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calzada M\u00e9xico-Xochimilco 101, Colonia San Lorenzo Huipulco, Tlalpan, Mexico City 14370, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Arenas-Rios","sequence":"additional","affiliation":[{"name":"Laboratorio de Morfofisiolog\u00eda y Bioqu\u00edmica del Espermatozoide, Departamento de Biolog\u00eda de la Reproducci\u00f3n, Universidad Aut\u00f3noma Metropolitana-Iztapalapa, Mexico City 09340, 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