Uteroplacental circulation and fetal vascular function and development

Abstract

Although blood flow in the placental vasculature is governed by the same physiological forces of shear, pressure and resistance as in other organs, it is also uniquely specialized on the maternal and fetal sides. At the materno-fetal interface, the independent uteroplacental and umbilicoplacental circulations must coordinate sufficiently to supply the fetus with the nutrients and substrates it needs to grow and develop. Uterine arterial flow must increase dramatically to accommodate the growing fetus. Recent evidence delineates the hormonal and endothelial mechanisms by which maternal vessels dilate and remodel during pregnancy. The umbilical circulation is established de novo during embryonic development but blood does not flow through the placenta until late in the first trimester. The umbilical circulation operates in the interest of maintaining fetal oxygenation over the course of pregnancy, and is affected differently by mechanical and chemical regulators of vascular tone compared to other organs. The processes that match placental vascular growth and fetal tissue growth are not understood, but studies of compromised pregnancies provide clues. The subtle changes that cause the failure of the normally regulated vascular processes during pregnancy have not been thoroughly identified. Likewise, practical and effective therapeutic strategies to reverse detrimental placental perfusion patterns have yet to be investigated.

Fig. 1.

Decreased uteroplacental perfusion in Japanese macaques fed a high fat diet (HFD). Maternal HFD leads to increased uterine artery pulsitility index (PI). A: Uterine artery (Uta) PI is 0.74 in a representative control (CTR) animal. B: The Uta PI is 1.17 in a representative HFD-Sensitive (HFD-S) animal with a Doppler waveform that demonstrates decreased diastolic flow consistent with increased vascular impedance when compared with A. C: The cQUta normalized to maternal weight was significantly reduced in HFD-Resistant (HFD-R) and HFD-S animals when compared with CTR. D: Uta PI is increased in HFD-S animals when compared with CTR. As a group, HFD (HFD-R + HFD-S) had a significant increase in Uta PI when compared with CTR. E: The cQUV normalized to fetal abdominal circumference was reduced in HFD-S animals when compared with controls. There was no difference in HFD-R animals when compared with controls. F: The umbilical artery (UA) PI was unaffected by diet group. * P < 0.05; CTR, n = 9; HFD-R, n = 6; HFD-S, n = 9. Reproduced, with permission [13].

Fig. 2.

Increases in peak resting oxygen consumption in pregnancy compared to pre-pregnancy values. Data from Metcalfe et al. [11].

Fig. 3.

Umbilical artery flow (cm/sec) changes in response to severe umbilicoplacental embolization in sheep. Rapid, repeated injections of microspheres into the umbilicoplacental circulation will induce fetal distress and umbilical artery flow patterns that parallel those seen in human IUGR. In this experiment, diastolic flow became absent 45 minutes after embolization, and reversed flow was evident 2 hours after embolization. Louey & Thornburg, unpublished data.

Fig. 4.

Fetal partial pressure of arterial oxygen during umbilicoplacental embolization (UPE) in sheep. Mean data for the control group (n=5) are shown by the continuous line ± SEM (shaded area). Mean ± SEM data for the UPE fetuses (n=5) are shown for the daily pre- (black circle, ●) and post-UPE periods (open circle, ○). Data modified from Louey et al. [80].