Prepubertal exposure to arsenic(III) suppresses circulating insulin-like growth factor-1 (IGF-1) delaying sexual maturation in female rats

Reprod Toxicol. 2014 Apr:44:41-9. doi: 10.1016/j.reprotox.2013.09.005. Epub 2013 Sep 30.


Arsenic (As) is a prevalent environmental toxin readily accessible for human consumption and has been identified as an endocrine disruptor. However, it is not known what impact As has on female sexual maturation. Therefore, in the present study, we investigated the effects of prepubertal exposure on mammary gland development and pubertal onset in female rats. Results showed that prepubertal exposure to 10 mg/kg of arsenite (As(III)) delayed vaginal opening (VO) and prepubertal mammary gland maturation. We determined that As accumulates in the liver, disrupts hepatocyte function and suppresses serum levels of the puberty related hormone insulin-like growth factor 1 (IGF-1) in prepubertal animals. Overall, this is the first study to show that prepubertal exposure to As(III) acts peripherally to suppress circulating levels of IGF-1 resulting in delayed sexual maturation. Furthermore, this study identifies a critical window of increased susceptibility to As(III) that may have a lasting impact on female reproductive function.

Keywords: Arsenic; Arsenite; Female puberty; Insulin-like growth factor-1 (IGF-1); Mammary gland development; Pubertal delay; Reproductive toxicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Arsenites / toxicity*
  • Environmental Pollutants / toxicity*
  • Estradiol / blood
  • Female
  • Growth Hormone / blood
  • Humans
  • Insulin-Like Growth Factor I / antagonists & inhibitors*
  • Insulin-Like Growth Factor I / metabolism
  • Liver / drug effects
  • Liver / pathology
  • Luteinizing Hormone / blood
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / growth & development
  • Maternal-Fetal Exchange
  • Pregnancy
  • Rats, Sprague-Dawley
  • Sexual Maturation / drug effects*
  • Sexual Maturation / physiology


  • Arsenites
  • Environmental Pollutants
  • insulin-like growth factor-1, rat
  • Estradiol
  • Insulin-Like Growth Factor I
  • Luteinizing Hormone
  • Growth Hormone
  • arsenite