Protein restriction during fetal and neonatal development in the rat alters reproductive function and accelerates reproductive ageing in female progeny

摘要

Recent studies demonstrate long-term programming of function of specific organ systems resulting from suboptimal environments during fetal life and development up to weaning. Nutrient restriction during pregnancy and lactation impairs overall fetal growth and development. We determined the effects of maternal protein restriction (MPR; 50% normal protein intake) during fetal development and/or lactation in rats on the function and ageing of the reproductive system of female progeny. Rats were fed either a control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. After delivery mothers received either C or R diet until weaning to provide four groups, CC, RR, CR and RC. We report data on female offspring only. After weaning pups were fed the C diet. MPR increased maternal progesterone, corticosterone, oestradiol and testosterone concentrations at 19 days gestation. Reproductive and somatic phenotype was altered as pup birth weight was decreased, and ano-genital distance was increased by MPR. Pup corticosterone was decreased at 2 days postnatal (PN) life. Vaginal opening and timing of the first oestrus were delayed in RR and CR and these differences were not related to body weight. At 21 days PN oestradiol in RR and CR and progesterone in RR were reduced; at 70 days PN luteinizing hormone (LH) in all restricted groups was reduced in dioestrus while follicle stimulating hormone (FSH) was unchanged. Cycle length increased between 140 days and 1 year in RR and CR but remained unchanged in CC, providing evidence of premature ageing of reproductive function. Fertility rates declined over the same period in the three experimental groups but not CC. MPR in one of the two experimental periods, either pregnancy or lactation, resulted in decreased pup survival compared with CC and RR. These data show that MPR results in delayed sexual maturation and premature ageing of reproductive function.