Oxidative-Stress-Mediated Epigenetic Dysregulation in Spermatogenesis: Implications for Male Infertility and Offspring Health

Genes, Journal Year: 2025, Volume and Issue: 16(1), P. 93 - 93

Published: Jan. 17, 2025

Male reproductive health is governed by an intricate interplay of genetic, epigenetic, and environmental factors. Epigenetic mechanisms—encompassing DNA methylation, histone modifications, non-coding RNA activity—are crucial both for spermatogenesis sperm maturation. However, oxidative stress, driven excessive reactive oxygen species, disrupts these processes, leading to impaired function male infertility. This disruption extends epigenetic resulting in abnormal gene expression chromatin remodeling that compromise genomic integrity fertilization potential. Importantly, oxidative-stress-induced alterations can be inherited, affecting the fertility offspring future generations. review investigates how stress influences regulation reproduction modifying RNAs, ultimately compromising spermatogenesis. Additionally, it discusses transgenerational implications disruptions their potential role hereditary infertility disease predisposition. Understanding mechanisms vital developing therapeutic strategies mitigate damage restore homeostasis germline. By integrating insights from molecular, clinical, research, this work emphasizes need targeted interventions enhance prevent adverse outcomes progeny. Furthermore, elucidating dose–response relationships between changes remains a critical research priority, informing personalized diagnostics interventions. In context, studies should adopt standardized markers damage, robust clinical trials, multi-omic approaches capture complexity Such rigorous investigations will reduce risk disorders optimize outcomes.

Language: Английский

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Mitogen-Activated Protein Kinase Phosphatase-2 Deletion Promotes Hyperglycemia and Susceptibility to Streptozotocin-Induced Diabetes in Female Mice In Vivo

Cells, Journal Year: 2025, Volume and Issue: 14(4), P. 261 - 261

Published: Feb. 12, 2025

The development of type 2 diabetes (T2D) is largely dependent on the maintenance pancreatic islet function and mass. Sexual dimorphism in T2D evident many areas, such as pathophysiology, treatment, prevention. Mitogen-activated protein kinase phosphatase-2 (MKP-2) has a distinct role regulation cell proliferation metabolic disorders. However, whether there causal relationship between MKP-2 onset unclear. aim this study was to determine whole-body glucose homeostasis impact using streptozotocin-induced injury. Here, we show that female mice with deletion exhibit hyperglycemia mouse models treated multiple low doses streptozotocin (STZ). In comparison, both male wild-type knockout were hyperglycemic. Consistent hyperglycemia, MKP-2-deficient exhibited reduced size. Under conditions, display enhanced JNK ERK phosphorylation associated downregulation genes important for function, Pdx-1 MafA. Furthermore, found impaired flux adipose tissue consistent dysfunctional pancreas. results Akt activation increased adiposity insulin resistance KO mice. These studies demonstrate critical vivo. This suggests may have gender-specific development. discovery raises possibility postmenopausal prevention benefit from activity cells.

Language: Английский

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Research Advances on the Role of Insulin-Like Peptides in Physiological States and Diseases

Advances in Clinical Medicine, Journal Year: 2025, Volume and Issue: 15(04), P. 1741 - 1747

Published: Jan. 1, 2025

Language: Английский

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Impact of Type 1 Diabetes on Testicular Microtubule Dynamics, Sperm Physiology, and Male Reproductive Health in Rat

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4579 - 4579

Published: May 10, 2025

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 microtubule-associated proteins (MAPs) in testis spermatozoa (SPZ). Using streptozotocin-induced T1D rat model, we examined expression localization key MAPs, Microtubule Affinity-Regulating Kinase 4 (MARK4), Microtubule-Associated Protein 1A (MAP1A), Dynein Light Chain LC8-Type (DYNLL1), Prolyl Endopeptidase (PREP), Radial Spoke Head 6 Homolog A (RSPH6A), alongside sperm functional parameters. Our findings showed that significantly impaired distribution these proteins, which may affect MTs organization be associated with cytoskeletal disorganization, germ cell differentiation. Moreover, rats exhibited reduced count, viability, motility, accompanied increased DNA fragmentation chromatin defects. Elevated levels 4-hydroxy-2-nonenal (4-HNE), marker OS, were detected SPZ, particularly acrosome flagellum, correlating mitochondrial dysfunction ATP depletion. Additionally, decreased intracellular Ca2+ levels, downregulation Cation Channel Sperm (CATSPER) Voltage-Dependent Anion 3 (VDAC3), altered tubulin acetylation, possibly due imbalanced Alpha-Tubulin N-Acetyltransferase (ATAT1) Histone Deacetylase (HDAC6) expression, also motility. The combined data suggest linked disrupted dynamics, contribute testicular quality, potentially affecting fertility. better understanding associations support development therapeutic strategies mitigate reproductive consequences improve fertility outcomes.

Language: Английский

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Unraveling the impact of semaglutide in a diabetic rat model of testicular dysfunction: Insights into spermatogenesis pathways and miRNA-148a-5p

Steroids, Journal Year: 2024, Volume and Issue: unknown, P. 109537 - 109537

Published: Nov. 1, 2024

Language: Английский

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