The pregnant sheep as a model for human pregnancy

Abstract

Successful outcome of human pregnancy not only impacts the quality of infant life and well-being, but considerable evidence now suggests that what happens during fetal development may well impact health and well-being into adulthood. Consequently, a thorough understanding of the developmental events that occur between conception and delivery is needed. For obvious ethical reasons, many of the questions remaining about the progression of human pregnancy cannot be answered directly, necessitating the use of appropriate animal models. A variety of animal models exist for the study of both normal and compromised pregnancies, including laboratory rodents, non-human primates and domestic ruminants. While all of these animal models have merit, most suffer from the inability to repetitively sample from both the maternal and fetal side of the placenta, limiting their usefulness in the study of placental or fetal physiology under non-stressed in vivo conditions. No animal model truly recapitulates human pregnancy, yet the pregnant sheep has been used extensively to investigate maternal-fetal interactions. This is due in part to the ability to surgically place and maintain catheters in both the maternal and fetal vasculature, allowing repeated sampling from non-anesthetized pregnancies. Considerable insight has been gained on placental oxygen and nutrient transfer and utilization from use of pregnant sheep. These findings were often confirmed in human pregnancies once appropriate technologies became available. The purpose of this review is to provide an overview of human and sheep pregnancy, with emphasis placed on placental development and function as an organ of nutrient transfer.

Figure 1

Schematic representation of pregnant sheep in vivo preparation used to measure the metabolism of the gravid uterus and fetus simultaneously. Infusate can be into either the maternal or fetal circulation, and blood samples can be drawn from either circulation simultaneously.

Figure 2

Schematic representation of maternal artery, uterine vein, umbilical vein and fetal arterial oxygen tensions during late gestation in human and sheep pregnancies.

Figure 3

Schematic representation of maternal artery, uterine vein, umbilical vein and fetal arterial oxygen tensions in late gestation normal and severe FGR sheep pregnancies. Note the reductions in fetal oxygenation and the elevated PO₂ in the uterine vein, indicative of reduced placental oxygen extraction.

Figure 4

Schematic representation of maternal and fetal oxygen content (mMol/L) values for late gestation human and sheep growth restricted pregnancies.