84 DEVELOPMENTAL EFFECTS OF CHOLESTEROL-ENRICHED HYPERLIPIDIC DIETS IN RABBITS

Abstract

The long-term effects of low birth weight on the onset of adult metabolic diseases have been described in several species. Low birth weight is usually due to maternal food restriction or placental insufficiency during pregnancy. In contrast, the effects of maternal high planes of nutrition or dietary unbalance have been less studied. In previous work, we have shown that the administration of a hypercholesterolemic (0.2%) hyperlipidic (8%) diet to rabbit does throughout puberty and subsequent pregnancy significantly affected fetal and postnatal development of their offspring. The aim of this study was to determine the relative role of cholesterol and of the n3/n6 fatty acid ratio on fetal development using the same model. Twenty-five does were fed from 10 weeks of age with 1 of 5 diets: S or SC (soy oil, 9% lipids, n3/n6 = 0.15 without or with 0.1% cholesterol), R or RC (rapeseed, 8% lipids, n3/n6 = 0.38 without or with 0.1% cholesterol), or Co (2% lipids, no cholesterol). Does were bred at 18 weeks of age. The growth of 4 fetuses per dam was monitored by weekly ultrasound scanning (Chavatte-Palmer P et al. 2008 Theriogenology). All pups were weighed at birth. Additionally, fetuses and placentas from a further 2 to 4 does per treatment group were collected at 15 days of pregnancy. Data were analyzed by ANOVA using group, number of fetuses, and dam as variables. Because different measurements were taken at different stages, the analysis of repeated measures could not be performed. Although maternal lipid intake was significantly increased in all treated groups, does adjusted their intake so that caloric intake and doe body weight were not statistically different between groups. Mean litter size was not different between groups. Group and, to a lesser extent, dam, but not litter size, significantly affected fetal development. Conceptus length was reduced on Day 9 of pregnancy in SC (–14%) and RC (–5%) compared with Co (P < 0.05). Fetal length was reduced on Day 15 in groups RC and S (both –9%, P < 0.05) but not in SC. Fetal abdominal perimeter measurements were smaller in SC, RC, and R at Day 22 and in SC at Day 28 (P < 0.05). Birth weight was decreased in all groups (–10, –18, –21, and –7% in SC, S, RC, and R, respectively compared with Co). Postmortem analyses did not show significant differences in fetal weight at Day 15, but placentas were significantly heavier in S compared with all other groups (P < 0.05). In conclusion, long-term cholesterol- and lipid-enriched diets induced intrauterine growth retardation in does with variable effects according to the n3/n6 fatty acid ratio and cholesterol dietary content, with more significant effects observed in the cholesterol-enriched diets. These effects are observed very shortly after implantation, indicating that oocyte and/or embryonic development may be affected. Further work is in progress to evaluate these early effects, using micro-array analysis of gene expression in the embryos.