Impact of maternal prenatal stress on growth of the offspring

Abstract

Unperturbed fetal development is essential for future health of an individual. Previous studies have linked diseases of aging to harmful alterations that happen during fetal development. Given the significant long-term impact that intrauterine environment has on an individual's life, it was hypothesized that maternal stress during pregnancy will have negative effects on the offspring's prenatal and postnatal growth. To test this, twenty-eight female and seven male Wistar rats (Rattus norvegicus) were purchased and bred to produce 176 offspring. During pregnancy, dams were randomly divided into four groups (n=7, per group) and immobilization stress induced as follows; Group 1 (GW1): immobilization stress on days 1-7 of pregnancy, Group 2 (GW2): on days 8-14, Group 3 (GW3): on days 15-21, Group 4 (Controls): left undisturbed. Maternal cortisol hormone, food intake, and weight gain were monitored during pregnancy. Pups were raised under normal laboratory conditions and sacrificed at ages: 4, 8, 12, and 16 weeks to determine the effect of prenatal stress. At necropsy, the tibia was removed and processed for histology. Differences among groups were determined by T-test or analysis of variance (ANOVA). Linear regression analysis was performed to establish the relationship between stress in utero and indicators of bone development in offspring. P values ≤ 0.05 were considered significant. Cortisol hormone levels in controls were lower than those of stressed animals. Stressed dams consumed 12.5% less food per day compared to controls. Animals in GW1 and GW2 gained less weight during pregnancy but had larger litters than did GW3 or the control group. Offspring born to GW3 were heavier compared to all other groups. GW3 offspring had a higher rate of bone formation. In conclusion, stress during pregnancy resulted in increased cortisol and reduced food intake in mothers, but faster growth and higher weight gain in offspring compared to controls.

Keywords: elevated cortisol; offspring development; prenatal stress.

Figure 1.

Maternal weight gain during pregnancy. A. Comparison of maternal gestational weight gain in GW1, GW2, GW3 and Control mothers. The figure shows the results of one-way ANOVA of weight by maternal group. The side points of each diamond are connected by a horizontal line at the mean of each group. The top and bottom diamond points are the upper and lower 95% confidence points of each group. B. Comparison for all pairs of means of maternal gestational weight gain using Tukey-Kramer (HSD). The Tukey-Kramer (HSD) added comparison circles to the plot and statistically compared each pair of means. There is a circle for each group with a horizontal diameter that aligns with its group mean. Circles with the same color are not statistically different while those with different colors represent groups with statistically different means.

Figure 2.

Cortisol (stress) hormone levels in dams during pregnancy. Cortisol hormone levels measured and quantified as micrograms per gram of feces (μg/g) in: A. Control mothers during pregnancy week 1 and GW1 mothers; B. Control mothers during pregnancy week 2 and GW2 mothers; C. Control mothers during pregnancy week 3 and GW3 mothers; D. Control mothers from day 1 to 20 of gestation.

Figure 3.

Overall comparison of means of cortisol hormone levels between control and stressed mothers, Litter size and Offspring weight gain. A. Overall comparison of means of cortisol hormone levels from all control mothers and all stressed mothers during pregnancy; B, Correlation between the number of pups bornand weight (in grams) gained by the mother during pregnancy; C, Mean weight (ingrams) of male offspring at age 4, 8, 12 and 16 weeks; D, Mean weight (in grams) of female offspring at age 4, 8, 12 and 16 weeks.

Figure 4.

The changes in histomorphormetric measurements at age 4, 8, 12 and 16 weeks in GW3 offspring (dashed line) and control offspring (solid line). A. Total tissue area (mm²); B. Bone area (mcm); C. Bone perimeter (mm); D. Osteoblast surface (mm); E, Osteoid surface (mm); F. Number of osteoclasts (N.Oc/mm); G, Eroded surface (mm); H. Upper zone of the growth plate (containing resting and proliferative cells) (mcm); I. Lower zone of the growth plate (containing hypertrophic cells) (mcm).