Department of Physiological Sciences, Center of Biological Sciences, Londrina State University, Londrina, PR, Brazil.
Department of Physiology, São Paulo State University, Botucatu, SP, Brazil.
Reprod Toxicol. 2019 Aug;87:1-7. doi: 10.1016/j.reprotox.2019.04.009. Epub 2019 May 2.
Metformin (MET) is a widely-used drug for the treatment of type 2 diabetes mellitus and gestational diabetes. It is known that metformin crosses the placenta and can to be transferred through milk. In vitro studies show that MET decreases gonadotropin-releasing hormone and gonadotropins release in rat neurons, and decreases progesterone and estradiol in rat granulosa cells and androstenedione synthesis in human theca cells. This study evaluated whether MET maternal exposure might interfere with reproductive parameters of female offspring. Wistar female rats were treated with MET 293 mg/kg/day, by gavage, from gestational day (GD) 0 to GD 21 (METG) or GD 0 until lactation day (LD) 21 (METGL). Controls groups received water. An increase in plasmatic estradiol levels was observed during the estrus stage in the METGL group. This result suggests that exposure to MET during gestational and lactational periods might be related to programming in theca and/or granulosa cells during development.
二甲双胍（MET）是一种广泛用于治疗 2 型糖尿病和妊娠糖尿病的药物。已知二甲双胍可以穿过胎盘，并通过乳汁转移。体外研究表明，MET 可减少大鼠神经元中促性腺激素释放激素和促性腺激素的释放，并减少大鼠颗粒细胞中的孕激素和雌二醇以及人卵巢膜细胞中的雄烯二酮合成。本研究评估了母体暴露于 MET 是否会干扰雌性后代的生殖参数。Wistar 雌性大鼠通过灌胃从妊娠第 0 天（GD）至第 21 天（METG）或从妊娠第 0 天至哺乳期第 21 天（METGL）每天接受 293mg/kg 的 MET 治疗。对照组给予水。在 METGL 组的发情期观察到血浆雌二醇水平升高。这一结果表明，在妊娠和哺乳期暴露于 MET 可能与发育过程中卵巢膜和/或颗粒细胞的编程有关。
