150 EFFECT OF MATERNAL OBESITY ON PERICONCEPTION FERTILITY AND BLASTOCYST GENE EXPRESSION IN THE MOUSE MODEL

Abstract

Obesity is frequently associated with infertility in humans and domestic animals. In this study, we aimed to study the effect of diet-induced obesity on oestrus cyclicity, ovulation rate, pre-implantation embryo development and blastocysts gene expression. Twenty-one NIH Swiss female mice were divided in 2 groups: one fed with a control diet (C, n = 9) and the other with a diet high in fat (F, n = 12) for 12 weeks. Dams were naturally bred and killed 3.5 days post-coitum. Bodyweight, numbers of corpora lutea and embryos and days required to breed the dams were recorded. Blastocysts were recovered and snap frozen in groups representing the individual dams. Expression of 10 candidate genes was analysed relative to H2afz. Data (means ± standard error of the means) were analysed by ANOVA (P < 0.05, significant). Five mice in the F group failed to breed during 20 days. These acyclic animals were significantly heavier than the other 7 of the F group (53.8 ± 3.8 vs 41.6 ± 0.9 g), with 4 weighting over 50 g. The seven cyclic animals in the F group showed a higher weight (41.6 ± 0.9 vs 31 ± 0.8 g) and higher number of days to mate (7.3 ± 1.6 vs 2.9 ± 0.5) compared with group C, but ovulation rates did not differ and reflected final blastocyst recovery. The expression level of 5 genes (Insr, Igf1r, Igf2r, Adipor1 and Adipor2) encoding for receptors of hormones related to metabolism regulation did not differ among groups. Two genes with roles in glucose (Scl2a1) and lipid transport (Ldlr) were down-regulated in the F group compared with the C group (Scl2a1: 1 ± 0.1 vs 1.38 ± 0.1; Ldlr: 1 ± 0.1 vs 1.24 ± 0.1); however, there were no differences in expression of the genes Gapdh (which encodes an essential glycolytic enzyme), Cpt1a (whose product catalyzes the rate limiting step of β-oxidation) and Sod2 (which encodes the mitochondrial isoform of superoxide dismutase). These results suggest that diet-induced obesity in the mouse model reduces fertility through oestrus cyclicity, blocking or prolonging the oestrus cycle, but there was no effect on ovulation rate or embryo development in those females that ovulated. The down-regulation of 2 genes related to nutrient uptake (Slc2a1 and Ldlr) in the F group suggests a protective mechanism to abate the excess of nutrients. Such protection may be effective, as the expression of genes for key metabolic markers for anaerobic glycolysis, fatty acid metabolism and oxidative stress remained unaltered.

Supported by Lalor Foundation to P. Bermejo-Alvarez, HD21896 to R. M. Roberts and RC1 ES018195 to C. S. Rosenfeld.