Maternal psychological stress-induced developmental disability, neonatal mortality and stillbirth in the offspring of Wistar albino rats

Abstract

BackgroundStress is an inevitable part of life, and maternal stress during the gestational period has dramatic effects in the early programming of the physiology and behavior of offspring. The developmental period is crucial for the well-being of the offspring. Prenatal stress influences the developmental outcomes of the fetus, in part because the developing brain is particularly vulnerable to stress. The etiology of birth defects of the offspring is reported to be 30–40% genetic and 7–10% multifactorial, with the remaining 50% still unknown and also there is no clear cause for neonatal mortality and still-birth.ObjectiveThe present study explores the association of maternal psychological stress on mother and the offspring’s incidence of birth defects, stillbirth, and neonatal mortality.Study designPregnant animals were restrained to induce psychological stress (3 times per day, 45 minutes per session). Except control group, other animals were exposed to restraint stress during the gestational period: early gestational stress (EGS, stress exposure during 1st day to 10th days of gestational period), late gestational stress (LGS, stress exposure during 11th day to till parturition), and full term gestational stress (FGS, stress exposure to the whole gestational period). The effects of maternal stress on the mother and their offspring were analyzed.ResultsExpectant female rats exposed to stress by physical restraint showed decreased body weight gain, food intake, and fecal pellet levels. Specifically, the offspring of female rats subjected to late gestational and full term gestational restraint stress showed more deleterious effects, such as physical impairment (LGS 24.44%, FGS 10%), neonatal mortality (EGS 2.56%, LGS 24.44%, FGS 17.5%), stillbirths (FGS 27.5%), low birth weight (EGS 5.42g, LGS 4.40g, FGS 4.12g), preterm births (EGS 539 Hrs, LGS 514 Hrs, FGS 520.6 Hrs), and delayed eyelid opening (EGS 15.16 Days, LGS 17 Days, FGS 17.67 Days).ConclusionThe results of this study reveal that maternal stress may be associated with the offspring’s abnormal structural phenotyping, preterm birth, stillbirth and neonatal mortality.

Prenatal two-hit stress affects maternal and offspring pregnancy outcomes and uterine gene expression in rats: match or mismatch?†

“…This is consistent with other research in rodents as well as our previous multigenerational model where shorter pregnancy duration was only visible as of the F1 pregnancies [35,72]. In contrast, other studies demonstrated that prenatal restraint or immune stress reduces pregnancy duration in the parental generation [73,74]. It is possible that the stressors applied are not intense enough and in order to deliver early, these animals would need an additional hit, for instance by having the added effect of altered maternal behavior on pregnancy outcomes, as we have seen in prior studies [35,47].…”

“…In like manner, maternal stress quite consistently leads to decreased weight gain during pregnancy in most animal models with respect to the metabolic effects of antenatal adversity [35,74,75]. Gestation however is considered a state of physiological hyperphagia to meet the increased energy demands of both mother and fetus [76].…”

Decidual cell FKBP51–progesterone receptor binding mediates maternal stress–induced preterm birth

“…Moreover, combined maternal and fetal deficiency of the Fkbp5 gene prevents such stress-mediated PTB. Consistent with our findings, Govindaraj et al also showed that late restraint stress (three times/day and 45min/each) from E11 to parturition, but not early onset stress from E1 to E11, shortened gestation in pregnant rats, indicating that the restraint stress model is a reliable inducer of PTB among different rodent species (62). Moreover, while P4 levels decline earlier in both stressed and unstressed wild-type mice compared to stressed and unstressed Fkbp5 −/− mice, stress-induced PTB does not appear to result from a premature decline in serum P4 (Fig.…”

Associations between maternal social support and stressful life event with ventricular septal defect in offspring: a case-control study

“…For example, it was reported that exogenous corticosteroid use during pregnancy could pose a small increased risk of birth defects [20]. There might be the possibility that increased production of corticosteroids in response to maternal stress exposure may play a role in VSD of offspring [21]. Moreover, there is an increasing evidence for the transgenerational impact of early-life experiences and the involvement of epigenetic pathways in these effect modifications [22].…”