Department of Veterinary Medicine, Federal Rural University of Pernambuco, Recife, Pernambuco, Brazil.
Department of General Biology, Federal University of Viçosa, Viçosa, Minas Gerais, Brazil.
Int J Exp Pathol. 2022 Oct;103(5):174-189. doi: 10.1111/iep.12446. Epub 2022 Jun 23.
Type 2 diabetes mellitus (T2D) during pregnancy is characterized by high levels of reactive oxygen species and pro-inflammatory factors in the placenta. Once these reactive species reach the foetus, they trigger physiological adaptations that allow the foetus to survive, but programme the organism to develop metabolic disorders in adulthood. The male reproductive system is highly susceptible to foetal programming. This study aimed to investigate the effects of intrauterine exposure to T2D on testicular histomorphometry and redox homeostasis of adult rats and evaluate the effects of maternal treatment with metformin and pentoxifylline. Female rats were induced to T2D, then treated with metformin and pentoxifylline, or co-treated with both drugs. The females were mated, the male offspring were sacrificed on postnatal day 90, and the testicles were collected for analysis. Metformin protected the tubular compartment, with the maintenance of the Sertoli cell population and daily sperm production. Pentoxifylline attenuated the effects of diabetes on Leydig cells, in addition to stimulating testosterone production and lowering lipid peroxidation. Intrauterine exposure to T2D results in important testicular alterations that compromise gonadal function, and the co-treatment with metformin and pentoxifylline may represent a promising therapy that attenuates these effects by combining the positive influences in both the tubular and interstitial compartments of the testicular parenchyma.
妊娠期 2 型糖尿病（T2D）的特征是胎盘内高水平的活性氧和促炎因子。一旦这些活性物质到达胎儿，它们就会引发生理适应，使胎儿能够存活，但会使机体在成年后发展出代谢紊乱。男性生殖系统对胎儿编程高度敏感。本研究旨在探讨宫内暴露于 T2D 对成年大鼠睾丸组织形态计量学和氧化还原平衡的影响，并评估母体用二甲双胍和己酮可可碱治疗的效果。将雌性大鼠诱导至 T2D，然后用二甲双胍和己酮可可碱治疗，或两种药物联合治疗。雌性大鼠交配，雄性后代在出生后第 90 天被处死，收集睾丸进行分析。二甲双胍保护管状区，维持支持细胞群体和每日精子生成。己酮可可碱除了刺激睾酮产生和降低脂质过氧化外，还减轻了糖尿病对间质细胞的影响。宫内暴露于 T2D 会导致重要的睾丸改变，损害性腺功能，二甲双胍和己酮可可碱联合治疗可能是一种有前途的治疗方法，通过结合睾丸实质的管状和间质区的积极影响来减轻这些影响。
