Differential oxidative stress induction and lethality of rat embryos after maternal exposure tot-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.

Glutathione redox dynamics and expression of glutathione-related genes in the developing embryo

“…Variations in E h and concentrations of GSH define discrete windows of development: unfertilized oocytes, embryos undergoing primary organogenesis, embryos undergoing organ differentiation, and growth of the larvae. Understanding the ontogeny of GSH redox potential in the embryo will help to identify periods of susceptibility to redox perturbations and critical windows of sensitivity to sources of oxidative stress or glutathione depletion [17, 102–104]. Moreover, ontogenic changes in the expression of GSH-related genes support the hypothesis that GSH redox states are tightly regulated early in development.…”

Prenatal immobility stress: Relationship with oxidative stress, inflammation, apoptosis, and intrauterine growth restriction in rats

“…A significant decrease was observed in Group V in terms of both the number and weight of fetuses compared to Groups III and IV. The duration of exposure to stress is closely related to the severity of adverse effects such as decrease in the number and weight of the fetus (Shivananjappa & Muralidhara., 2013).…”

“…A significant increase in placental MDA levels was reported in preeclampsia and diabetes models, which are experimental models with intrauterine growth retardation, which is consistent with our study (Erşahin et al, 2016). Similar results have been reported in stress models created by chemical agent exposure (El‐Dakdoky, 2015; Shivananjappa & Muralidhara., 2013).…”

“…Apoptosis, cell proliferation, and differentiation must occur in a balanced way for the normal development of the placenta. The provision of homeostasis in the tissue depends on the preservation of the apoptosis‐proliferation balance (El‐Dakdoky, 2015; Shivananjappa & Muralidhara., 2013; Zhu et al, 2019). It has been reported in clinical studies that apoptosis and apoptosis‐related protein expressions were increased in the placental tissues of mothers whose fetuses were diagnosed with intrauterine growth retardation and preeclampsia, compared to healthy placental tissue (Allaire et al, 2000; Isaksen et al, 2004).…”

Phospholipid peroxidation-driven modification of chondrogenic transcription factor mediates alkoxyl radicals-induced impairment of embryonic bone development

“…During maternal stress, various species of free radicals can be formed through endogenous oxidative stress response and exogenous stimuli, like ionising radiation, ultraviolet radiation, drugs, carcinogenic compounds, and environmental pollutants, among others [ [19] , [20] , [21] , [22] ]. Of these species, alkoxy radicals play a key role in triggering lipid peroxidation by furnishing PUFA hydroperoxides, which further accelerate the propagation of free radical initiated chain reactions [ 23 ].…”