title: Differential oxidative stress induction and lethality of rat embryos after maternal exposure to t-butyl hydroperoxide during postimplantation period.
abstract: 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 GD(5-7) or GD(8-10)) at dosages of [one tenth the median lethal dose (LD(50)) and one fifth LD(50)/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 GD(13) 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 GD(5-7) was relatively higher, compared with GD(8-10), 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.
authors.affiliation: Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, Karnataka, India.
authors.forename: Mahesh Mysore
authors.initials: MM
authors.lastname: Shivananjappa
authors.lastname: Muralidhara
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D016877:Oxidants / Q000008:administration & dosage / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020122:tert-Butylhydroperoxide / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D016877:Oxidants; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide; D005978:Glutathione