Oxidative stress and DNA damage in utero and embryo implantation of mice exposed to carbon disulfide at peri-implantation

Abstract

Carbon disulfide (CS2) has reproductive toxicity but the mechanism remains unclear. The aim of the present study was to investigate the effect of oxidative stress and DNA damage on embryo implantation of mice exposed to CS2 at peri-implantation. CS2 exposure was on gestational day 3 (GD3), GD4, GD5 and GD6, separately, and the number of embryonic day 9 (E9) mouse embryos was obtained. DNA damage of endometrial cells, oxidative stress and 8-hydroxy-2′-deoxyguanosine (8-OH-dG) level in uterus tissues were tested with time series at different end points after exposure. The number of E9 mouse embryos significantly decreased in all CS2 exposure groups, especially on GD4 exposure. The rates of embryo implantation decreased by 43.05%, 63.74%, 60.45% and 47.26% for CS2 exposure on GD3, GD4, GD5 and GD6, respectively. Oxidative stress significantly increased within 24 h and reached the top level at 18 h after exposure. The same time-dependent trend was observed no matter when the exposure happened at peri-implantation. 8-OH-dG significantly increased at 18 h and 24 h after exposure by 893.8% and 647.4%, respectively, when compared with the control. The indexes of DNA damage significantly increased at 6 h after exposure, which appeared earlier than the changes of oxidative stress and 8-OH-dG. Besides, both oxidative stress and DNA damage showed a strong negative correlation with the number of E9 mouse embryos. The present study illustrated that CS2 directly induced DNA damage in endometrial cells and enhanced the action through oxidative stress, both of which were responsible for CS2-induced embryo loss.