Dulaglutide rescues the elevated testicular dysfunction in a mouse model of high-fat diet-induced obesity

• Published in: Mutation research. Genetic toxicology and environmental mutagenesis 2024-08, Vol.898, p.503805, Article 503805
• Main Authors: Attia, Sabry M., Alshamrani, Ali A., Ahmad, Sheikh F., Albekairi, Norah A., Nadeem, Ahmed, Attia, Mohamed S.M., Ansari, Mushtaq A., Alqahtani, Faleh, Bakheet, Saleh A., Harisa, Gamaleldin I.
• Format: Article
• Language: English
• Subjects: Animals; Chromosome Aberrations - drug effects; Diet, High-Fat - adverse effects; Disease Models, Animal; DNA Damage - drug effects; DNA strand breaks; Glucagon-like peptide-1 analogs; Glucagon-Like Peptides - analogs & derivatives; Glucagon-Like Peptides - pharmacology; Glucagon-Like Peptides - therapeutic use; Hypoglycemic Agents - pharmacology; Immunoglobulin Fc Fragments - pharmacology; Male; Mice; Mice, Inbred C57BL; Obesity - drug therapy; Obesity complications; Oxidative stress; Recombinant Fusion Proteins - pharmacology; Sperm Motility - drug effects; Spermatozoa - drug effects; Testicular Diseases - drug therapy; Testis - drug effects; Testis - metabolism; Testis - pathology
• ISSN: 1383-5718; 1879-3592; 1879-3592
• DOI: 10.1016/j.mrgentox.2024.503805

Obesity is a well-known risk factor for testicular function; however, dulaglutide's effect on the testis in obesity has received little attention. Currently, clinicians prescribe the antidiabetic drug dulaglutide only off-label for weight management in non-diabetics. Investigating the impact of this novel compound on obesity is critical for determining whether it has any disruptive effects on testicular cells. We used a well-known animal model of high-fat diet-induced obesity in this investigation, and testicular dysfunction was determined by sperm DNA damage, spermatocyte chromosomal abnormalities, and spermiogram analysis. Following a 12-week high-fat diet challenge, mice were randomly assigned to dulaglutide (0.6 mg/kg/day) or saline treatments for five weeks. Testes and sperm cells were collected 24 h after the last dulaglutide injection. Untreated obese mice had a lower testes/body weight ratio, more sperm DNA damage, diakinesis-metaphase I chromosomal abnormalities, a lower sperm count/motility, more cell morphological defects, and an altered testicular redox balance. In obese mice, dulaglutide injection efficiently restored all disturbed parameters to their control levels. Dulaglutide injection into healthy mice exhibited no significant harmful effects at the applied regimen. As a result, we infer that dulaglutide therapy might bring obese men additional benefits by recovering testicular dysfunction induced by obesity. •Obese mice showed higher testicular damage than normal mice.•Dulaglutide exhibited no significant harmful effects at the applied regimen.•Dulaglutide can alleviate testicular abnormalities induced by obesity.•Dulaglutide reduces testicular dysfunction by reducing raised oxidative stress.