Academic Journal
The link between diabetes and male infertility: mechanisms and implications.
| Τίτλος: | The link between diabetes and male infertility: mechanisms and implications. |
|---|---|
| Συγγραφείς: | Haffez H; Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Capital University (Formerly Helwan University), Cairo, 11795, Egypt. hesham.haffez@pharm.capu.edu.eg.; Center of Scientific Excellence 'Helwan Structural Biology Research, (HSBR)', Capital University (Formerly Helwan) Helwan University, Cairo, 11795, Egypt. hesham.haffez@pharm.capu.edu.eg.; Capital University (Formerly Helwan University), Cairo, 11795, Egypt. hesham.haffez@pharm.capu.edu.eg., Mosaad M; Benha Fertility and ICSI Centre, Qalyubia, 13511, Egypt., Rezk AY; Obstetrics & Gynecology Department, Faculty of Medicine, Benha University, Qalyubia, 13511, Egypt., Sayed A; Genomics Research Program, Children's Cancer Hospital 57357, 11562, Cairo, Egypt., Hassan ZA; Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Capital University (Formerly Helwan University), Cairo, 11795, Egypt. |
| Πηγή: | Scientific reports [Sci Rep] 2026 Jul 24; Vol. 16 (1). Date of Electronic Publication: 2026 Jul 24. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : Nature Publishing Group, copyright 2011- |
| Ιατρικοί όροι (MeSH): | Infertility, Male*/metabolism , Infertility, Male*/etiology , Infertility, Male*/pathology , Diabetes Mellitus*, Testosterone/blood ; Luteinizing Hormone/blood ; Glycated Hemoglobin/metabolism ; Follicle Stimulating Hormone/blood ; Spermatozoa/metabolism ; Spermatozoa/pathology ; Caspase 3/metabolism ; Humans ; Male ; Apoptosis ; Adult ; DNA Fragmentation ; Sperm Motility ; Semen Analysis |
| Περίληψη: | Diabetes mellitus (DM) is a growing global health crisis affecting male reproductive function, yet the enhanced combined effects of diabetes with pre-existing fertility abnormalities remain poorly understood. This study aims to investigate the individual and combined effects of diabetes and abnormal semen parameters on male reproductive function and the underlying apoptotic mechanisms. Thirty-nine men were enrolled and stratified into two phases: a validation cohort (nondiabetic vs. diabetic; fertile vs. abnormally infertile) and a four-group mechanistic study (normal nondiabetic (n = 10), abnormal nondiabetic (n = 11), normal diabetic (n = 10), and abnormal diabetic (n = 8)). We assessed HbA1c, FSH, LH, testosterone, semen parameters, sperm apoptosis (Annexin V/PI flow cytometry), DNA fragmentation (diphenylamine), and expression of apoptotic markers (caspase-3, cytochrome c, Bax, and Bcl-2) at gene and protein levels. Diabetic patients had significantly higher HbA1c (9.6 ± 2.31% vs. 5.49 ± 0.42%, p < 0.001), elevated FSH and LH, and reduced testosterone. Abnormal infertile patients showed impaired motility and morphology. The abnormal diabetic group had the most severe dysfunction: lowest rapid progressive motility (11.3 ± 3.10%, p < 0.001 vs. control) and highest early apoptosis (58.9 ± 8.79%, p < 0.0001). Protein analysis showed a pro-apoptotic shift with an elevated Bax/Bcl-2 ratio (3.64), increased cytochrome-c, and caspase-3 activation exclusively in this group (p < 0.0001). Diabetes and abnormal semen parameters exert enhanced combined detrimental effects on male fertility via enhanced activation of the intrinsic mitochondrial apoptotic pathway. Diabetic men with pre-existing fertility abnormalities exhibit the most severe phenotype and require prioritized clinical intervention. (© 2026. The Author(s).) |
| Competing Interests: | Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study was conducted in accordance with the ethical principles of the Declaration of Helsinki and Good Clinical Practice guidelines. The study protocol was approved by the Faculty of Pharmacy, Capital University (formerly Helwan University) Ethics Committee (Approval No. 02H2022). All participants provided written informed consent after receiving detailed information about the study objectives, procedures, potential risks, and benefits. Participants were assured of confidentiality and their right to withdraw at any time without affecting their medical care. |
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| Contributed Indexing: | Keywords: Apoptosis; Diabetes mellitus; Hormones; Male infertility; Semen |
| Substance Nomenclature: | 3XMK78S47O (Testosterone) 9002-67-9 (Luteinizing Hormone) 0 (Glycated Hemoglobin) 9002-68-0 (Follicle Stimulating Hormone) EC 3.4.22.- (Caspase 3) |
| Entry Date(s): | Date Created: 20260724 Date Completed: 20260724 Latest Revision: 20260927 |
| Update Code: | 20260927 |
| PubMed Central ID: | PMC13400617 |
| DOI: | 10.1038/s41598-026-63095-w |
| PMID: | 42498725 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2045-2322 |
|---|---|
| DOI: | 10.1038/s41598-026-63095-w |