Lactational exposure to hexavalent chromium delays puberty by impairing ovarian development, steroidogenesis and pituitary hormone synthesis in developing Wistar rats

Toxicol Appl Pharmacol. 2008 Oct 15;232(2):180-9. doi: 10.1016/j.taap.2008.06.002. Epub 2008 Jun 17.


Hexavalent chromium (Cr-VI) is used in a wide range of industries. Cr-VI from chromate industries and atmospheric emissions contribute to the Cr contamination in the environment. Cr is a reproductive metal toxicant that can traverse the placental barrier and cause a wide range of fetal effects including ovotoxicity. Therefore, the goal of this study was to investigate the basic mechanisms involved in Cr(VI)-induced ovotoxicity, and the protective role of vitamin C on ovarian follicular development and function in Cr(VI)-induced reproductive toxicity using both in vivo and in vitro approaches. Lactating rats received potassium dichromate (200 mg/L) with or without vitamin C (500 mg/L), through drinking water from postpartum days 1-21. During postnatal days (PND) 1-21 the pups received Cr(VI) via the mother's milk. Pups from both control and treatment groups were continued on regular diet and water from PND-21 onwards, and euthanized on PND-21, -45 and -65. Cr(VI) decreased steroidogenesis, GH and PRL, increased FSH and did not alter LH. Cr(VI) delayed puberty, decreased follicle number, and extended estrous cycle. Spontaneously immortalized rat granulosa cells were treated with 12.5 microM (IC(50)) potassium dichromate for 12 and 24 h, with or without vitamin C pre-treatment. Cr(VI) decreased the mRNA expressions of StAR, SF-1, 17beta-HSD-1, 17beta-HSD-2, FSHR, LHR, ER alpha and ER beta. Vitamin C pre-treatment protected ovary and granulosa cells from the deleterious effects of Cr(VI) toxicity, both in vivo and in vitro. Therefore, Cr(VI) toxicity could be a potential risk to the reproductive system in developing females, and vitamin C plays a protective role against Cr(VI)-induced ovotoxicity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Ascorbic Acid / administration & dosage
  • Cell Line
  • Chromium / administration & dosage
  • Chromium / toxicity*
  • Female
  • Gonadal Steroid Hormones / antagonists & inhibitors
  • Gonadal Steroid Hormones / biosynthesis
  • Gonadal Steroid Hormones / genetics
  • Lactation* / blood
  • Ovary / drug effects*
  • Ovary / growth & development*
  • Ovary / metabolism
  • Pituitary Hormones / antagonists & inhibitors
  • Pituitary Hormones / biosynthesis*
  • Pituitary Hormones / genetics
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Sexual Maturation / drug effects*
  • Sexual Maturation / physiology


  • Gonadal Steroid Hormones
  • Pituitary Hormones
  • Chromium
  • chromium hexavalent ion
  • Ascorbic Acid