The association between suboptimal intrauterine environment and developmental origins of adult health and disease is variable, suggesting that genotype may contribute to eventual outcome. The objective of this study was to characterize maternal and fetal responses to maternal dietary restriction during pregnancy in 2 phylogenetically distant strains of mice. Pregnant A/J (n=35) and C57BL/6J (B6) (n=36) mice underwent either a 30% dietary restriction (DR) from day 6.5 until day 17.5 of gestation or were fed ad libitum. Seven mothers from each strain and diet were randomly selected for dissection on day 18.5 to assess fetal body and organ weights and maternal endocrine status through the collection of serum to measure progesterone, corticosterone, cortisol, and estradiol levels. The remaining mice were allowed to deliver spontaneously to assess gestational effects. Both strains showed similar responses to maternal DR during pregnancy in terms of reductions in maternal weight gain during pregnancy, reductions in fetal body weight, increased pup death within 24 hours of birth, and decreased placental 11beta-HSD2 protein expression. The impact of maternal DR was greater in B6 mice than A/J when assessing reductions in fetal kidney weight, embryo-placenta ratio, increases in placental weight, fetal brain-liver ratio, and maternal corticosterone and cortisol levels. Moreover, preterm delivery was significantly increased in DR B6 mice compared to DR A/J mice. The observed strain variations in response to dietary restriction may offer a unique opportunity to investigate gene-environment interactions associated with developmental origins of adult health and disease.

The objective of this study was to characterize offspring responses to maternal dietary restriction (DR) in two phylogenetically distant strains of mice: A/J and C57BL/6J (B6). Pregnant mice were fed 100% or 70% of ad libitum between 6.5 and 17.5 days (d) gestation. Offspring were fed 100% ad libitum postweaning. All comparisons were made to strain and sex matched controls. Male DR-B6 offspring initially grew slower than controls; however, by 77d and 182d they were significantly heavier (P < 0.05). Further, they had an increase percentage fat mass (+70%, P < 0.01) by 182d and were glucose intolerant at both 80d (P < 0.001) and 186d (P < 0.05). In contrast, weight, %Fat mass and glucose tolerance in DR-A/J males during postnatal life were not different from controls. Female DR-B6 mice showed catch-up growth during the first 77d of life; however, their weight, %Fat mass and glucose tolerance were not different from controls at 80d and 186d. Although female DR-A/J were heavier than controls at 182d (P < 0.05), their %Fat mass and glucose tolerance were not different from controls at 182d and 186d. The observed strain and sex differences offer a unique opportunity to begin to define gene-environment interactions that contribute to developmental origins of health and disease.