Journal Article Epublish 6 citations
PubMed: 40429724 DOI: 10.3390/ijms26104579
Impact of Type 1 Diabetes on Testicular Microtubule Dynamics, Sperm Physiology, and Male Reproductive Health in Rat.
Int J Mol Sci 26(10)
Authors: Alessandra Biasi, Maria Rosaria Ambruosi, Maria Zelinda Romano, Serena Boccella, Sara Falvo, Francesca Guida, Francesco Aniello, Sabatino Maione, Massimo Venditti, Sergio Minucci
Affiliations
- Dipartimento di Medicina Sperimentale, Università degli Studi della Campania "Luigi Vanvitelli", 80138 Napoli, Italy.
- Dipartimento di Science e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università degli Studi della Campania "Luigi Vanvitelli", 81100 Caserta, Italy.
- Dipartimento di Biologia, Università degli Studi di Napoli "Federico II", 80126 Napoli, Italy.
Abstract
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 Ca 2+ 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.
MeSH
Diabetes Mellitus, Cells, Microtubule-Associated Proteins, Sperm Motility, Physiology, Fertility, Reproductive Health, Oxidative Stress, Spermatogenesis, Spermatozoa, Microtubules, Diabetes Mellitus, Type 1