132 - pQCT Analysis of Cortical and Trabecular Bone in Rats Exposed to High Levels of Cortisol In-Utero

Poster Board Number: 132
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Abstract Body : Introduction: Unperturbed fetal development is essential for the 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 bone density and cross-sectional area.

Methods: To test this hypothesis, 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 femur was removed and preserved for image analysis. The femurs were scanned using the XCT Research SA+ peripheral Quantitative Computed Tomography (pQCT). Mixed models were fit to the data to assess the effects of maternal stress, sex and side on offspring over the 16-week duration of the study. Specifically, the following responses were recorded: cortical density, cortical area, trabecular density, and trabecular area. The analyses were performed in R.

Results:
Cortical density: In males, maternal stress in-utero did not have a significant impact on cortical density of the offspring. In females, maternal stress induced during week three of gestation had a significant negative effect on cortical density of the offspring. The smaller cortical density was evident at the age of 8 weeks and 12 weeks. However, by the age of 16 weeks, all groups had relatively similar density.

Cortical area: In both males and females, GW3 offspring had a significantly higher cortical area at the age of 4 weeks and 16 weeks compared to all the other groups.

Trabecular density: In both males and females maternal stress did not have a significant impact on trabecular density. Interestingly, there was evidence of side dominance in this analysis. At the age of 4 weeks and 8 weeks, trabecular density on the right side was higher in males. At the age of 12 weeks, trabecular density was higher on the left side but by the age of 16 weeks both sides were relatively equal in males.

Trabecular area: In males, GW3 offspring had a higher trabecular area compared to all the other groups at the age of 4 weeks. By the age of 8, this difference was not apparent. In females the maternal stress did not have a significant impact on trabecular area in the offspring.

Conclusion: In this study, in-utero stress was found to negatively impact cortical density in females at the age of 8 weeks and 12 weeks while males are shown to have thrived regardless of increased exposure to cortisol levels in-utero. Offspring exposed to maternal stress in-utero during week three of their development interestingly had higher cortical area and trabecular. This is consistent with histological data that found GW3 offspring to have a higher bone formation rate and higher weight gain which could be because of an altered metabolism.