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Induction of intrauterine growth restriction by reducing placental vascular growth with the angioinhibin TNP-470

Rutland, CS, Mukhopadhyay, M, Underwood, S, Clyde, N, Mayhew, TM and Mitchell, Christopher (2005) Induction of intrauterine growth restriction by reducing placental vascular growth with the angioinhibin TNP-470. BIOLOGY OF REPRODUCTION, 73 (6). pp. 1164-1173. [Journal article]

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DOI: 10.1095/biolreprod.105.043893


The placenta is a specialized vascular interface between the maternal and fetal circulations that increases in size to accommodate the nutritional and metabolic demands of the growing fetus. Vascular proliferation and expansion are critical components of placental development and, consequently, interference with vascular growth has the potential to severely restrict concurrent development of both the placenta and fetus. In this study, we describe the effects of an antiangiogenic agent, TNP-470, on placental vascular development and the induction of a form of intrauterine growth restriction (IUGR) in mice. Administration of TNP-470 to dams in the second half of pregnancy resulted in a smaller maternal weight gain accompanied by decreased placental and fetal sizes in comparison with control animals. Total numbers of fetuses per litter were not affected significantly. Stereological analysis of placentas revealed no changes in the combined lengths of vessels. However, the mean cross-sectional areas of maternal and fetal vessels in the labyrinth of TNP-470-treated mice were reduced at Embryonic Day 13.5 (E13.5) but not at E18.5. Further analysis showed reduced placental endothelial proliferation at E13.5 and E18.5 in TNP-470-treated animals. No other structural or morphometric differences in placentas were detected between TN P-470-treated and control mice at E18.5. This study provides conclusive evidence that administration of TNP-470 interferes with placental vascular proliferation and vessel caliber and results in a reproducible model of IUGR.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Genomic Medicine
ID Code:9469
Deposited By: Professor Christopher Mitchell
Deposited On:23 Jan 2010 16:03
Last Modified:10 May 2017 10:51

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