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子宫内和哺乳期暴露于二甲双胍会导致雄性大鼠后代的生殖系统改变。

In utero and lactational exposure to metformin induces reproductive alterations in male rat offspring.

机构信息

Department of Physiological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, PR, Brazil.

Department of Physiological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, PR, Brazil.

出版信息

Reprod Toxicol. 2017 Dec;74:48-58. doi: 10.1016/j.reprotox.2017.08.023. Epub 2017 Sep 1.

Abstract

Metformin (MET) is prescribed for the treatment of type 2 diabetes mellitus and gestational diabetes. Although MET crosses the placenta, it is considered safe throughout gestation. However, it has been shown in humans that maternal exposure to MET increases sex hormone binding globulin levels in newborns, and in rats it decreases the testosterone concentration at gestational day (GD) 16.5. Therefore, the present study evaluated if maternal exposure to MET could interfere with reproductive parameters of male offspring. Wistar female rats were treated with MET 293mg/kg/day, by gavage from GD0 to GD21 (METG) or GD0 until lactational day (LD) 21 (METGL) and the control groups received water. Sexual behavior of male offspring was affected in both MET groups. However, a decrease in the sperm count was observed only in METGL group. These results suggest that MET exposure induced alterations in reproductive parameters of male offspring in adulthood depending on exposure time.

摘要

二甲双胍(MET)用于治疗 2 型糖尿病和妊娠糖尿病。虽然 MET 可以穿过胎盘,但在整个妊娠期内被认为是安全的。然而,人类研究表明,母体暴露于 MET 会增加新生儿的性激素结合球蛋白水平,而在大鼠中,它会降低妊娠第 16.5 天的睾酮浓度。因此,本研究评估了母体暴露于 MET 是否会干扰雄性后代的生殖参数。Wistar 雌性大鼠从 GD0 到 GD21 (METG)或 GD0 到哺乳期第 21 天(METGL)每天通过灌胃给予 293mg/kg 的 MET,而对照组给予水。雄性后代的性行为在两个 MET 组中均受到影响。然而,仅在 METGL 组观察到精子计数减少。这些结果表明,MET 暴露会根据暴露时间影响雄性后代成年后的生殖参数。

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