-
Views
-
Cite
Cite
Roza D. Yunusova, Raymond P. Aitken, John S. Milne, Pawel Piotr Borowicz, Lawrence P. Reynolds, Joel S. Caton, Dale A. Redmer, Jacqueline M. Wallace, Influence of Maternal Dietary Intake, Intrauterine Growth Restriction (IUGR), and Estrogen Replacement on Placental Development and Vascularity., Biology of Reproduction, Volume 85, Issue Suppl_1, 1 July 2011, Page 801, https://doi.org/10.1093/biolreprod/85.s1.801
Close - Share Icon Share
Overnourished pregnant adolescent sheep are characterized by feto-placental growth restriction and attenuated peripheral reproductive steroid concentrations. Herein the effects of excess maternal intake, IUGR, and 17beta-estradiol (E2) replacement therapy during mid-gestation on placental cell proliferation, angiogenic gene expression and vascularity were investigated. Singleton pregnancies were established by embryo transfer, and adolescent dams offered a control diet (C, n = 12, 100% requirement), or high diet (H, n = 28, 2 x C) throughout gestation. From d 50 to 90, E2 (0.05 mg i.m.) was administered twice daily to 14 H ewes (H+E2). Two H+E2 ewes subsequently miscarried. At necropsy (d 130), mean±sd fetal weight in C was 4435 ± 422 g and IUGR in H groups was defined as weight at least 2 standard deviations below the C mean (< 3591 g) corresponding to 8 of 14 H and 5 of 12 H+E2 pregnancies. Data were analysed for effects of excess maternal intake, IUGR, and E2 replacement. Excess maternal intake decreased placentome and fetal weights (P < 0.001) but increased fetal:placental weight ratio (P < 0.001). Placentome weight in IUGR was 42% lower than in non-IUGR (P < 0.001) but independent of E2 replacement. Placental tissues (caruncles [CAR] and cotyledons [COT]) were collected for mRNA analysis (n=14 genes) or perfusion fixed for vascular quantification. H diet decreased (P < 0.08) cell proliferation across the whole placentome, decreased (P < 0.06) COT FLT1 and CAR ANGPT1 mRNA and increased (P < 0.09) area per capillary in CAR. IUGR pregnancies had increased ANGPT1 (P < 0.03) and NOS3 (P < 0.08) expression in COT and higher VEGF (P < 0.09), FLT1 (P < 0.08) and NOS3 (P < 0.02) mRNA in CAR compared to non-IUGR. This upregulation of angiogenic factors in IUGR may reflect placental adaptation to improve fetal nutrient delivery and is supported by a greater fetal:placental weight ratio in IUGR vs. non-IUGR (P < 0.001). E2 supplementation had no effect on COT mRNA but in CAR, NOS3 mRNA expression was greater in both H+E2 and H+E2 IUGR groups, (P < 0.04 and P < 0.01, respectively) indicating a putative and persistent effect of E2 on nitric oxide mediated vasodilation some 40 days after treatment ceased. Within ewes carrying IUGR fetuses those who received E2 in mid-pregnancy had decreased (P < 0.09) ANGPT2 and 3 fold higher NOS3 mRNA expression (P < 0.01) in CAR. In conclusion, we have demonstrated variable effects of excess maternal intake and IUGR status on placental cell proliferation, angiogenic gene expression, and vascular development which may underlie the reported changes in both placental growth and weight specific efficiency observed previously for dietary intake and confirmed here for both intake and IUGR. While E2 supplementation did increase peripheral maternal concentrations as designed, the limited responsiveness to mid-gestational replacement suggests either that E2 in isolation does not have a major impact on placental growth and vascular development or that the timing of treatment was not optimal for effects to persist until late gestation. Research is supported by NIH grant R01HD045784.
(poster)
