Placental and fetal hepatic growth are selectively inhibited by prolonged reductions of uterine blood flow in pregnant sheep

Abstract

Experiments were conducted in eight pregnant sheep to determine the effect on fetal growth of mechanical restriction of uterine blood flow (RUBF) between 120 days and 134 days gestation. Uterine blood flow measured in the middle uterine arteries was 40% less in RUBF animals compared with control animals at the end of the experimental period. There was no change in fetal blood gases, bodyweights, or organ weights between the two groups of animals. The rate of DNA synthesis in the right lobe of the liver was significantly less in RUBF animals (581 +/- 34 dpm micrograms-1 DNA) compared with control animals (845 +/- 44 dpm microgram-1 DNA). There was no difference in the rate of DNA synthesis in the left lobe of the liver or in any of the other organs examined. Autoradiographic examination of the placental cotyledons demonstrated that most DNA synthesis in the placenta was occurring in fetal trophoblastic cells and there was a 40% reduction in the nuclear-labelling index of placental trophoblast cells. These studies show that mild mechanical reductions in uterine blood flow in pregnant sheep results in the selective inhibition of growth in the right lobe of the fetal liver and the placental trophoblastic cells. The mechanism underlying this close association remains to be determined.

Fetal Growth Restriction Is Associated With Prioritization of Umbilical Blood Flow to the Left Hepatic Lobe at the Expense of the Right Lobe

“…Indeed, a direct relationship between venous liver perfusion and tissue proliferation was demonstrated in fetal sheep (4). Our findings suggest that this will affect predominantly the right lobe and, interestingly, fetal lambs exposed to reduced uterine blood flow selectively show reduced growth of the right lobe of the liver (17). Selective right liver lobe damage was also reported in human fetuses that have suffered intrauterine asphyxia (18).…”

Hepatic Artery Hemodynamics Suggest Operation of a Buffer Response in the Human Fetus

“…It is the main site for hematopoiesis until the end of the second trimester, when a shift to the bone marrow occurs (Mikkola et al 2005). Both liver growth and hematopoiesis seem to be affected by its perfusion (McLellan et al 1995;Rocheleau et al 1999;Kunisaki et al 2006).…”

Three‐dimensional Sonographic Measurement of Liver Volume in the Small‐for‐Gestational‐Age Fetus

“…The liver occupies most of the upper abdominal cavity, and it is the first organ to be affected by intrauterine growth restriction (IUGR). 3 Fetal liver weight is reduced in animal models of IUGR [4][5][6][7] ; therefore, direct measurements of fetal liver size may enhance early detection of the fetus at risk of IUGR. 8 There have been a few human studies that have directly measured liver length (LL) by using traditional two-dimensional (2D) sonography in SGA fetuses, and the results have been conflicting.…”