Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá (UEM), Av. Colombo, 5790, CEP: 87020-900 Maringá, Paraná, Brazil; Department of Anatomy, Institute of Biomedical Science III, University of São Paulo (USP), Av. Prof. Lineu Prestes, 2415, CEP: 05508-000 São Paulo, São Paulo, Brazil.
Department of Biotechnology, Genetics, and Cell Biology, State University of Maringá (UEM), Av. Colombo, 5790, CEP: 87020-900 Maringá, Paraná, Brazil.
Toxicol Appl Pharmacol. 2021 Oct 15;429:115712. doi: 10.1016/j.taap.2021.115712. Epub 2021 Sep 2.
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.
二甲双胍（Met）被广泛用于控制血糖水平，作用于包括生殖组织在内的各种器官，以改善生殖和寿命。本研究评估了新生期 Met 暴露是否可以预防成年期超重引起的雄性生殖功能障碍。随机选择 Wistar 大鼠幼仔，从出生后第 1 天（PND）至第 12 天，每天接受腹腔注射生理盐水（Sal；0.9% NaCl/天，2 mL/kg）或 Met（100 mg/kg/天，2 mL/kg）。从 PND 60 至 90 天，动物接受常规（R；4.5%脂肪；Sal R 和 Met R 组）或高脂肪（HF；35%脂肪；Sal HF 和 Met HF 组）饮食。在 PND 90 天，所有动物被安乐死，以评估其生物计量和生殖参数。接受 R 饮食的 Sal 和 Met 组体重相似，但 HF 饮食增加了两组的体重。Sal HF 组睾丸抗氧化状态和附睾尾部炎症谱显示出损伤。HF 饮食减少了 Leydig 和 Sertoli 细胞数量，精子质量下降。Met R 动物表现出积极的生殖编程，这是由于抗氧化防御、炎症生物标志物和精子形态的改善。Met HF 预防了 HF 饮食对生殖器官和精子形态的损害，但对精子活力没有影响。早期 Met 暴露对成年大鼠的雄性生殖系统产生积极影响，预防生殖 HF 障碍。新颖性和意义的陈述：二甲双胍用于控制 2 型糖尿病，可改善代谢和寿命。建议在怀孕期间避免使用二甲双胍，但在哺乳期使用该药物时没有信息。这是我们第一次在这项当前研究中表明，二甲双胍在雄性生殖组织中发挥积极作用，并有助于后期生活。这些数据显示，与生理盐水动物相比，二甲双胍动物的抗氧化防御和抗炎谱更好，可能直接改善生殖器官形态生理学和精子形态。此外，新生期 Met 的应用编程雄性生殖以抵消后期肥胖环境对生殖器官的损害。
