Neonatal metformin short exposure inhibits male reproductive dysfunction caused by a high-fat diet in adult rats
| Autor: | Glaura Scantamburlo Alves Fernandes, Lucas Paulo Jacinto Saavedra, Gláucia Eloisa Munhoz de Lion Siervo, Stephanie Carvalho Borges, Marialba Avezum Alves de Castro Prado, Gessica Dutra Gonçalves, Henrique Rodrigues Vieira, Kesia Palma-Rigo, Carina Previate, Josana Klagenberg, Milene Aparecida Bobato de Melo, Ananda Malta, Paulo Cezar de Freitas Mathias, Nilza Cristina Buttow, Vander Silva Alves, Camila Quaglio Neves |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_treatment media_common.quotation_subject Intraperitoneal injection Anti-Inflammatory Agents Physiology Overweight Diet High-Fat Toxicology medicine.disease_cause Antioxidants Drug Administration Schedule Testis medicine Animals Lactation Testosterone Rats Wistar Saline Sperm motility media_common Pharmacology Pregnancy business.industry Reproduction medicine.disease Metformin Oxidative Stress Animals Newborn Inflammation Mediators medicine.symptom business Oxidative stress medicine.drug |
| Zdroj: | Toxicology and Applied Pharmacology. 429:115712 |
| ISSN: | 0041-008X |
| DOI: | 10.1016/j.taap.2021.115712 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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