Strain Differences in the Impact of Dietary Restriction on Fetal Growth and Pregnancy in Mice

Abstract

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.