Exploring the Omic Impacts of Obesity and Diabetes on the Male Reproductive System: A Translational Study

• Grant number: 24/19049-4
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2025
• End date: August 31, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Fabiana Ferreira de Souza
• Grantee: Fabiana Ferreira de Souza
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Camila Renata Corrêa ; Débora Cristina Damasceno ; Marcos Gomides Carvalho ; Thaís Regiani Cataldi ; Thaisy Tino Dellaqua ; Vania dos Santos Nunes Nogueira

Abstract

This study aims to understand the molecular mechanisms involved in male infertility caused by diabetes and obesity, emphasizing the need for an integrated approach to identify therapeutic targets. For this, the study will be conducted on Wistar rats (males: n=80) and men (n=20), divided into a control (C), obese (Ob), diabetic (Di) and obese-diabetic (ObDi) groups. The rats will be obtained from the Experimental Research Unit (UNIPEX, UNESP, Botucatu) with induced and validated illnesses. The selection of male volunteers will be based on inclusion criteria (BMI of 25 kg/m² and fasting blood glucose between 70 and 100 mg/dL [C], 30 kg/m² [Ob or ObDi] and >200 mg /dL [Di or ObDi], aged between 20 and 50 years and sexual abstinence for 2 days before collection, at the Clinic of Endocrinology (adults) of the FMB, UNESP, Botucatu Once the illnesses were confirmed and after obtaining free and clear consent of the men, a sample of blood (serum) and ejaculate will be obtained. The rats will be euthanized, the blood will be collected by cardiac puncture, the epididymis will be used to obtain sperm and the testicles will be dissected for histopathology and immunohistochemistry for androgen and insulin receptors (n=40). Serum from rats and humans will be used to measure serum concentrations of leptin, adiponectin, ghrelin, insulin, glucose, testosterone, LH and FSH. The sperm will be analyzed for kinetics, concentration, morphology and DNA fragmentation and then prepared for proteomics (humans: seminal plasma and sperm) and metabolomics (humans: sperm and seminal plasma; rats: sperm) by mass spectrometry (ESI-QTof MS/MS). Western blotting will be used to validate protein abundance. The remaining rats (males: n=40 and females: n=40) will be used for in vitro fertility test, in which embryo outcome will be evaluated, including cleavage rate, blastocyst formation and morphological classification according to development. The results of this multidisciplinary approach are expected to provide a deeper understanding of the molecular mechanisms involved and possible therapeutic strategies to address the impacts of obesity and diabetes on male reproductive health. (AU)