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

Date Published: February 21, 2017

Publisher: Public Library of Science

Author(s): Sakthivel Govindaraj, Annadurai Shanmuganathan, Ravindran Rajan, Fatima Crispi.


Stress 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.

The present study explores the association of maternal psychological stress on mother and the offspring’s incidence of birth defects, stillbirth, and neonatal mortality.

Pregnant 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.

Expectant 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).

The results of this study reveal that maternal stress may be associated with the offspring’s abnormal structural phenotyping, preterm birth, stillbirth and neonatal mortality.

Partial Text

Maternal stress not only affects the mother, but also affects the developing fetus, and may have long-lasting effects, eventually affecting their subsequent progeny [1]. Stress exposure during the gestational period has potential adverse effects on the developing fetus, which may contribute to the early onset of many pathological conditions [2]. The developing fetal brain is more vulnerable to stress, which may cause abnormal phenotypes, both structurally and functionally [3]. Maternal stress has been shown to lead to birth defects [4], with both studies from animal models and human patients demonstrating stillbirth and infant mortality [5][6] in the offspring when exposed to stress during gestational period. In the present study, it has been observed that when female Wistar albino rats are exposed to restraint stress during their gestational period, their offspring have lower birth weights, and greater incidences of neonatal mortality, still birth, and birth defects.

As per general perception, dams will increase their food intake during the progression of pregnancy to meet the nutritional needs of the growing fetus. However, an extensive variation in the food intake of pregnant dams during gestation was observed in the present study. The maternal food intake of the control animals was increased when compared to stress-exposed groups from the 1st day to 10th day of gestational period. EGS and FGS groups (i.e., the groups exposed to stress by restraint the animal between the 1st and 10th day of gestation) showed decreased food intake, which may be due to increased GC levels. Previous studies reported that higher circulating levels of GC can positively stimulate gluconeogenesis and liver metabolism, thereby inhibiting food intake. The LGS group was not exposed to restraint-stress during the 1st to 10th day of gestational period, and accordingly showed increased food intake during that time. Additionally, the LGS and FGS groups, which were exposed to restraint stress from the 11th day to parturition, showed decreased food intake, which may also be due to the increased gluconeogenesis process, liver metabolism and alterations in hypothalamic appetite hormone levels during stress [12]; in contrast, the EGS group showed increased food intake on late gestational period. It was further confirmed by De Vos et al. that subcutaneous administration of a pharmacological dose of hydrocortisone (1, 10 and 100 μg/g/day) causes a decrease in body weight and food consumption [15].

The developing fetus is highly sensitive to adverse effects experienced by the mother, as the developing fetal brain is more plastic and has a poor ability to respond and adapt to maternal stress. Maternal stress affects the fetus by elevating the secretion of glucocorticoids and increasing the placental GC levels, which may lead to the stimulation of gluconeogenesis and the inhibition of glucose uptake by peripheral tissues, decrease in protein synthesis, increase in muscle wasting and the inhibition of calcium intake for bone formation, all of which may cause a decrease in maternal food intake, fecal pellets levels, and maternal body weight gain during the gestation period. Therefore, the elevation of glucocorticoids in maternal restraint stress may cause stillbirth, neonatal mortality, birth defects, decreased birth weight, postnatal development and delayed eyelid opening. Further studies are warranted to understand the underlying molecular mechanisms and structural and functional analysis of the gestational restraint stress induced adverse effects. The present study shows maternal stress exposure during gestational period has long term deleterious effects on the fetus development.




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