Biol Reprod Keystone Symposia Conference on Frontiers in Reproductive Biology & Regulation of Fertility.
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BOR - Papers in Press, published online ahead of print August 3, 2005.
Biol Reprod 2005, 10.1095/biolreprod.105.043893
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BIOLOGY OF REPRODUCTION 73, 1164–1173 (2005)
DOI: 10.1095/biolreprod.105.043893
© 2005 by the Society for the Study of Reproduction, Inc.

Research Article

Induction of Intrauterine Growth Restriction by Reducing Placental Vascular Growth with the Angioinhibin TNP-470

Catrin S. Rutland 2, Mallinath Mukhopadhyay 3, Suzanne Underwood 3, Norma Clyde 4, Terry M. Mayhew 2, and Christopher A. Mitchell 1 4

School of Biomedical Sciences,2 University of Nottingham, Nottingham, NG7 2UH United Kingdom School of Human Development,3 University of Nottingham, Nottingham, NG5 1PB United Kingdom School of Biomedical Sciences,4 University of Ulster, Coleraine, BT52 1SA United Kingdom

ABSTRACT

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 TNP-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.

blood vessel, developmental biology, embryo, endothelium, intrauterine growth restriction, mouse, placenta, pregnancy, proliferation, TNP-470, trophoblast

FOOTNOTES

1 Correspondence: Christopher A. Mitchell, Centre for Molecular Biosciences, School of Biomedical Science, University of Ulster at Coleraine, Cromore Road, Coleraine, Co. Londonderry, BT52 1SA, United Kingdom. FAX: 44 0 28 7032 4965; ca.mitchell{at}ulster.ac.uk






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Copyright © 2005 by the Society for the Study of Reproduction.