Proceedings of The Physiological Society

University of Cambridge (2008) Proc Physiol Soc 11, PC37

Poster Communications

Putative role for oestrogen as the missing link between nutrition and feto- placental growth restriction in overnourished adolescent sheep.

J. M. Wallace1, J. S. Milne1, R. P. Aitken1, L. P. Reynolds2, D. A. Redmer2

1. Rowett Research Institute, Aberdeen, United Kingdom. 2. Centre for Nutrition and Pregnancy, North Dakota State University, Fargo, North Dakota, USA.

Young pregnant growing adolescents are nutritionally sensitive as competition for nutrients exists between the mother and her developing fetus. This is replicated in the overnourished adolescent sheep, where high (H) dietary intakes to promote rapid maternal growth and adiposity are associated with premature delivery of low birth weight lambs relative to optimally nourished controls (C), where initial adiposity is maintained throughout. In overnourished dams, mid-gestation alterations in placental angiogenesis and uterine blood flow precede late onset placental growth restriction, which in turn limits fetal nutrient supply and growth (1). Exogenous oestrogen influences uterine vascular development and blood flow and may provide the missing link between nutrition and feto-placental growth. Here we investigated the relationship between dietary intake, maternal oestrogen concentrations and feto-placental mass. Singleton pregnancies to a single sire were established in adolescent ewes of equivalent age, weight and adiposity. In Expt.1, oestradiol-17β (E2) concentrations were determined in blood collected from C and H dams prior to necropsy at D50 or 75 of gestation (term=145days), and in ewes switched from H to C-intake at D50 and euthanized on D75 (n=11-13/group/stage). In Expt.2, blood was sampled from C and H dams at 28- day intervals from D0 to 140 and related to pregnancy outcome at term (n=12/group). In Expt.1, total placentome mass was equivalent in C and H at D50 and 75, but was increased by switching H ewes to C (average at D75; 557, 537 and 681g, respectively, P<0.05). Plasma E2 was low and independent of diet at D50. At D75, E2 was decreased in H (P<0.01) and increased in H-C (P<0.05) relative to C (mean ± sem, 1.9±0.16, 3.1±0.17, 2.6±0.15pg/ml, respectively). In Expt.2, gestation length (143±0.6 vs. 145±0.4days), fetal placental mass (279±13 vs. 473±28g) and lamb birth weight (3368±215 vs. 5631±216g) were lower in H than in C groups (P<0.05 to P<0.00001). E2 concentrations diverged by D84 and were 2-3 fold higher in C compared with H at D112 (3.2±0.27 vs. 10.3±1.15pg/ml) and D140 (5.0±0.44 vs. 12.7±1.34pg/ml, P<0.00005). Irrespective of dietary treatment, E2 concentrations at D112 (and D140) were positively correlated with gestation length (r=0.525, P<0.01), fetal placental mass (r=0.695, P<0.001) and lamb birth weight (r=0.780, P<0.001). Late gestation E2 concentrations were also negatively associated with maternal gestational live weight gain (r=-0.756, P<0.001), and may reflect differences in metabolic clearance rate as well as placental secretion. While these data are commensurate with the hypothesis that nutritionally-mediated suppression of oestrogen may partly underlie impaired feto-placental growth restriction in growing adolescents, definitive proof via E2 supplementation is required.

Where applicable, experiments conform with Society ethical requirements