Differential oxidative stress induction and lethality of rat embryos after maternal exposure to t-butyl hydroperoxide during postimplantation period

In mammals, reactive oxygen species (ROS) are essential factors for cell proliferation, differentiation, and growth,
notably during gestation, but are also potentially damaging agents. The present study describes the extent and pattern
of oxidative stress (OS) induction in maternal milieu, placenta, and embryos of rats after in vivo exposure to sublethal
doses of a well-known model prooxidant, such as t-butyl hydroperoxide (tbHP). tbHP administered (intraperitoneally)
to pregnant rats on specific gestation days (GDs) (either GD5–7 or GD8–10) at dosages of [one tenth the median lethal
dose (LD50) and one fifth LD50/day) caused significant OS, as evident by enhancement of malondialdehyde (MDA)
and ROS levels, depleted reduced glutathione levels and elevated protein carbonyl content in maternal liver and
kidney. Further, tbHP treatment also caused significant oxidative impairments in placenta, whereas the weights were
marginally increased. Further, tbHP treatment induced a higher incidence of embryonic lethality (4- to 6-fold higher
than controls) and induced marked OS among GD13 embryos, as evidenced by elevated MDA, ROS generation, altered
redox status, and enzymatic antioxidant defenses, suggesting the vulnerability of embryos. Interestingly, incidence
of embryonic mortality and degree of oxidative dysfunctions caused by tbHP treatment during GD5–7 was relatively
higher, compared with GD8–10, suggesting differential susceptibility of embryos during the early postimplantation
period. Based on these findings, it is hypothesized that critical windows during early gestation may account for the
differential susceptibility of developing embryos to pro-oxidants and necessitate a better understanding of this
embryonic response to pro-oxidant exposures.