DNA damage and apoptosis of endometrial cells cause loss of the early embryo in mice exposed to carbon disulfide

Toxicol Appl Pharmacol. 2013 Dec 1;273(2):381-9. doi: 10.1016/j.taap.2013.09.013. Epub 2013 Sep 29.

Abstract

Carbon disulfide (CS2) may lead to spontaneous abortion and very early pregnancy loss in women exposed in the workplace, but the mechanism remains unclear. We designed an animal model in which gestating Kunming strain mice were exposed to CS2 via i.p. on gestational day 4 (GD4). We found that the number of implanted blastocysts on GD8 was significantly reduced by each dose of 0.1 LD50 (157.85 mg/kg), 0.2 LD50 (315.7 mg/kg) and 0.4 LD50 (631.4 mg/kg). In addition, both the level of DNA damage and apoptosis rates of endometrial cells on GD4.5 were increased, showed definite dose-response relationships, and inversely related to the number of implanted blastocysts. The expressions of mRNA and protein for the Bax and caspase-3 genes in the uterine tissues on GD4.5 were up-regulated, while the expressions of mRNA and protein for the Bcl-2 gene were dose-dependently down-regulated. Our results indicated that DNA damage and apoptosis of endometrial cells were important reasons for the loss of implanted blastocysts induced by CS2.

Keywords: Apoptosis; Blastocyst implantation; Carbon disulfide; DNA damage; Endometrial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Carbon Disulfide / toxicity*
  • DNA Damage / drug effects
  • DNA Damage / physiology*
  • Embryo Loss / chemically induced*
  • Embryo Loss / pathology*
  • Endometrium / drug effects
  • Endometrium / pathology*
  • Female
  • Mice
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / pathology
  • Random Allocation

Substances

  • Carbon Disulfide