Effects of prenatal food restriction on reproductive function in adult female rats (911.13)

Abstract

The percentage of adults born low birth weight (LBW) is increasing due to advances in neonatal medicine. Studies in a variety of model organisms indicate that LBW offspring have global perturbations several physiological systems, making it likely that LBW offspring have impaired reproductive physiology. Therefore, we hypothesized that prenatal food restriction that produces LBW offspring would cause female hypothalamic pituitary gonadal (HPG) axis dysfunction as evidenced by differences in hypothalamic gonadotropin releasing hormone (GnRH), estrous cyclicity and age at puberty and reproductive senescence. In this study, pregnant rats were fed ad libitum or 50% of their normal caloric intake from e10 to e21, all pups were cross‐fostered to control dams and litters were culled to 8 pups. Female offspring weight and size from birth through lactation, age at puberty, estrous cyclicity and PND1 hypothalamic GnRH protein expression via western blot. Restricted offspring exhibited LBW (5.6±0.08vs.6.5±0.06, p<0.05). LBW offspring had earlier onset puberty (33.5±0.2vs.38.2±0.2, p<0.01) and significantly longer estrous cycles by PND90 (6.1±0.4vs.4.7±0.3, p<0.05). Although all control offspring had normal estrous cycles at 8 months of age, 80% of restricted offspring had stopped cycling. In addition, hypothalamic GnRH protein expression was decreased at PND1 in LBW offspring (1±0.1vs.0.5±0.1, p<0.05), suggesting that HPG axis dysfunction is present at birth. These data indicate that prenatal food restriction impedes neuroendocrine development and shortens female reproductive lifespan. Further studies are needed to provide a more complete picture of the consequences of LBW for female reproductive physiology.