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

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.

Keywords: Antidiabetic drug; Maternal exposure; Sexual behavior; Sperm count.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Female
  • Fertility / drug effects
  • Genitalia, Male / drug effects
  • Hypoglycemic Agents / toxicity*
  • Lactation
  • Male
  • Maternal-Fetal Exchange
  • Metformin / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats, Wistar
  • Sexual Behavior, Animal / drug effects
  • Sexual Maturation / drug effects
  • Sperm Count
  • Sperm Motility / drug effects
  • Spermatozoa / drug effects
  • Spermatozoa / physiology
  • Testosterone / blood

Substances

  • Hypoglycemic Agents
  • Testosterone
  • Metformin