SHEEP MODELS OF INTRAUTERINE GROWTH RESTRICTION: FETAL ADAPTATIONS AND CONSEQUENCES
Article first published online: 21 MAY 2008
© 2008 The Author. Journal compilation © 2008 Blackwell Publishing Asia Pty Ltd
Clinical and Experimental Pharmacology and Physiology
Volume 35, Issue 7, pages 730–743, July 2008
How to Cite
Morrison, J. L. (2008), SHEEP MODELS OF INTRAUTERINE GROWTH RESTRICTION: FETAL ADAPTATIONS AND CONSEQUENCES. Clinical and Experimental Pharmacology and Physiology, 35: 730–743. doi: 10.1111/j.1440-1681.2008.04975.x
- Issue published online: 21 MAY 2008
- Article first published online: 21 MAY 2008
- Received 15 December 2006; revision 22 November 2007; accepted 26 November 2007.
- cardiovascular system;
- intrauterine growth restriction;
- 1Intrauterine growth restriction (IUGR) has been associated with poor perinatal health outcomes. Animal models have been used to investigate why IUGR is associated with a poor prognosis. The sheep has been used extensively as an experimental model for IUGR with poor placental substrate supply to the fetus induced using a range of methods, including the surgical ablation of the majority of endometrial caruncles prior to conception, experimental induction of maternal hyperthermia, ligation of an umbilical artery or embolization of the placenta in late gestation and maternal overnutrition in the pregnant adolescent ewe.
- 2Fetal adaptations to fetal hypoxia and hypoglycaemia include activation of the fetal hypothalamic–pituitary–adrenal (HPA) axis and sympathetic nervous system and an associated increase in circulating cortisol and noradrenaline concentrations. Fetal cardiovascular responses vary according to the method used to induce placental dysfunction.
- 3Although an array of experimental models has been used to induce placental dysfunction at different stages of fetal development, each leads to remarkably similar fetal growth, metabolic, neuroendocrine and cardiovascular adaptations and consequences. The extent and range of the fetal physiological adaptations to chronic placental insufficiency are determined by the duration of exposure and the degree of the severity of substrate supply restriction.
- 4The present review summarizes how sheep models of IUGR have provided an increased understanding of the nature of the fetal adaptations to IUGR, their longer-term physiological consequences and how to improve clinical management of IUGR in human pregnancies.