{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:35:23Z","timestamp":1790868923662,"version":"4.1.0"},"reference-count":90,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T00:00:00Z","timestamp":1746835200000},"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>Type 1 diabetes (T1D) is a chronic metabolic disease defined by sustained hyperglycemia, leading to oxidative stress (OS) and systemic complications, including male subfertility. This study investigates the potential impact of T1D-induced OS on microtubule (MTs) dynamics and microtubule-associated proteins (MAPs) in the testis and spermatozoa (SPZ). Using a streptozotocin-induced T1D rat model, we examined the expression and localization of key MAPs, including Microtubule Affinity-Regulating Kinase 4 (MARK4), Microtubule-Associated Protein 1A (MAP1A), Dynein Light Chain LC8-Type 1 (DYNLL1), Prolyl Endopeptidase (PREP), and Radial Spoke Head 6 Homolog A (RSPH6A), alongside sperm functional parameters. Our findings showed that T1D significantly impaired the expression and distribution of these proteins, which may affect MTs organization and be associated with cytoskeletal disorganization, and impaired germ cell differentiation. Moreover, T1D rats exhibited reduced sperm count, viability, and motility, accompanied by increased DNA fragmentation and chromatin defects. Elevated levels of 4-hydroxy-2-nonenal (4-HNE), a marker of OS, were detected in SPZ, particularly in the acrosome and flagellum, correlating with mitochondrial dysfunction and ATP depletion. Additionally, decreased intracellular Ca2+ levels, downregulation of Cation Channel of Sperm (CATSPER) and Voltage-Dependent Anion Channel 3 (VDAC3), and altered tubulin acetylation, possibly due to imbalanced Alpha-Tubulin N-Acetyltransferase 1 (ATAT1) and Histone Deacetylase 6 (HDAC6) expression, were also associated with impaired sperm motility. The combined data suggest that T1D-induced OS is linked to disrupted MTs dynamics, which may contribute to testicular dysfunction and reduced sperm quality, potentially affecting male fertility. A better understanding of these associations may support the development of therapeutic strategies to mitigate the reproductive consequences of T1D and improve male fertility outcomes.<\/jats:p>","DOI":"10.3390\/ijms26104579","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T10:58:07Z","timestamp":1747047487000},"page":"4579","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Impact of Type 1 Diabetes on Testicular Microtubule Dynamics, Sperm Physiology, and Male Reproductive Health in Rat"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2742-1995","authenticated-orcid":false,"given":"Alessandra","family":"Biasi","sequence":"first","affiliation":[{"name":"Dipartimento di Medicina Sperimentale, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0193-4634","authenticated-orcid":false,"given":"Maria Rosaria","family":"Ambruosi","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9378-178X","authenticated-orcid":false,"given":"Maria Zelinda","family":"Romano","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Boccella","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Falvo","sequence":"additional","affiliation":[{"name":"Dipartimento di Science e Tecnologie Ambientali, Biologiche e Farmaceutiche, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Guida","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9640-2255","authenticated-orcid":false,"given":"Francesco","family":"Aniello","sequence":"additional","affiliation":[{"name":"Dipartimento di Biologia, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80126 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabatino","family":"Maione","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7357-5353","authenticated-orcid":false,"given":"Massimo","family":"Venditti","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1007-7840","authenticated-orcid":false,"given":"Sergio","family":"Minucci","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.12688\/f1000research.11421.1","article-title":"Cell polarity, cell adhesion, and spermatogenesis: Role of cytoskeletons","volume":"6","author":"Li","year":"2017","journal-title":"F1000Research"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.reprotox.2019.11.006","article-title":"Role of microtubule +TIPs and \u2212TIPs in spermatogenesis\u2014Insights from studies of toxicant models","volume":"91","author":"Mao","year":"2020","journal-title":"Reprod. 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