Neonatal metformin short exposure inhibits male reproductive dysfunction caused by a high-fat diet in adult rats.

Metformin (Met) is widely used to control blood glucose levels and acts on various organs, including reproductive tissues, to improve reproductive and lifespan. This study evaluated whether neonatal Met exposure prevented male reproductive dysfunction caused by being overweight during adulthood. Randomized Wistar rat pups received an intraperitoneal injection from postnatal days (PNDs) 1 to 12of saline (Sal; 0.9% NaCl/day in 2mL/kg) or Met (100 mg/kg/day in 2 mL/kg). From PNDs 60 to 90, the animals received a regular (R; 4.5% fat; Sal R and Met R groups) or a high-fat (HF; 35% fat; Sal HF and Met HF groups) diet. At PND 90, all animals were euthanized to evaluate their biometric and reproductive parameters. The Sal and Met groups with R showed similar body weights, however, the HF diet increased the body weight in both groups. The Sal HF group showed testicular damage regarding in antioxidant status and inflammatory profile in the epididymal cauda. The HF diet reduced Leydig and Sertoli cells numbers, with lower sperm quality. The Met R animals showed positive reproductive programming, due to improved antioxidant defense, inflammatory biomarkers, and sperm morphology. Met HF prevented HF diet damage to reproductive organs and sperm morphology, but not to sperm motility. Early Met exposure positively affected the male reproductive system of adult rats, preventing reproductive HF disorders. STATEMENT OF NOVELTY AND SIGNIFICANCE: Metformin is used to control type 2 diabetes mellitus and can act to improve metabolism and lifespan. Metformin avoidance is recommended during pregnancy, but there is no information regarding its use when breastfeeding. For the first time, we showed in this current study that metformin positively acts in the male reproductive tissues and helps involved in later life. These data showed a better antioxidant defense and anti-inflammatory profile of Metformin animals than Saline animals and might directly improve reproductive organs morphophysiology and sperm morphology. Also, the neonatal Met application programs the male reproduction to counterbalance damages from an obesogenic environment in later life.

Pulmonary Emphysema Impairs Male Reproductive Physiology Due To Testosterone and Oxidative Stress Imbalance in Mesocricetus auratus.

This study evaluated whether pulmonary emphysema affects sperm quality, male reproductive organs, and testosterone levels in adult male hamsters. Mesocricetus auratus males (130-150 g) were subdivided into a control group (C group) and an emphysema group (E group). The C group received an intratracheal instillation of saline solution (0.3 mL/100 g of body weight), and the E group received papain (40 mg/100 g of body weight). After 60 days, the biometric, pulmonary, and reproductive parameters of each group were evaluated. The E group developed pulmonary emphysema, which decreased body weight and sperm quality compared to the C group. In oxidative stress-related assays, lipid peroxidation was increased in the testis and epididymis (caput and cauda) in the E group compared with the C group. However, only the caput epididymis showed a reduction in glutathione levels. Pulmonary emphysema also affected the testicle by inducing an increase in abnormal seminiferous tubules, accompanied by a decrease in seminiferous epithelium height. Spermatogenesis kinetics were also modified by pulmonary emphysema. The number of Leydig and Sertoli cells decreased in the E group, accompanied by an increase in the nuclear volume of Leydig cells. Testosterone concentration was increased in the E group. Similarly, pulmonary emphysema altered epididymal components in all regions. In conclusion, pulmonary emphysema affected the reproductive system in this experimental model, as shown by testicular and epididymal morphophysiology changes, hormonal alteration, and oxidative stress imbalance, inducing the loss of correct function in the male reproductive system.