Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy

Abstract

Physiological conversion of the maternal spiral arteries is key to a successful human pregnancy. It involves loss of smooth muscle and the elastic lamina from the vessel wall as far as the inner third of the myometrium, and is associated with a 5-10-fold dilation at the vessel mouth. Failure of conversion accompanies common complications of pregnancy, such as early-onset preeclampsia and fetal growth restriction. Here, we model the effects of terminal dilation on inflow of blood into the placental intervillous space at term, using dimensions in the literature derived from three-dimensional reconstructions. We observe that dilation slows the rate of flow from 2 to 3m/s in the non-dilated part of an artery of 0.4-0.5mm diameter to approximately 10 cm/s at the 2.5mm diameter mouth, depending on the exact radius and viscosity. This rate predicts a transit time through the intervillous space of approximately 25s, which matches observed times closely. The model shows that in the absence of conversion blood will enter the intervillous space as a turbulent jet at rates of 1-2m/s. We speculate that the high momentum will damage villous architecture, rupturing anchoring villi and creating echogenic cystic lesions as evidenced by ultrasound. The retention of smooth muscle will also increase the risk of spontaneous vasoconstriction and ischaemia-reperfusion injury, generating oxidative stress. Dilation has a surprisingly modest impact on total blood flow, and so we suggest the placental pathology associated with deficient conversion is dominated by rheological consequences rather than chronic hypoxia.

Fig. 1

a) A photomicrograph of the human endometrium on the fourth day of menstruation showing an eroded spiral artery (arrowed) projecting freely into the uterine lumen. b) A photomicrograph of spiral arteries in a rhesus monkey during the phase of ovulation injected with India ink in gelatin. The arrow marks the endometrial–myometrial boundary, and a marked constriction (asterisked) can be seen in the spiral artery in the junctional zone just below. c) Reconstruction from serial sections of a converted spiral artery passing through the myometrium (M) and endometrium (E) before opening into the intervillous space through the basal plate of a term placenta. The widest dimension of the opening is given as 2.4 mm. Reproduced from Refs. , and respectively with permission of the Carnegie Institute of Washington.

Fig. 2

Diagrammatic representation of uterine and placental vasculature (red shading = arterial; blue shading = venous) in the non-pregnant, pregnant and immediate post-partum state. Normal pregnancy is characterized by the formation of large arterio-venous shunts that persist in the immediate post-partum period. By contrast pregnancies complicated by severe preeclampsia are characterized by minimal arterio-venous shunts, and thus narrower uterine arteries. Extravillous cytotrophoblast invasion in normal pregnancy (diamonds) extends beyond the decidua into the inner myometrium resulting in the formation of funnels at the discharging tips of the spiral arteries. Contrast with severe preeclampsia. (Prepared by Ms. Leslie Proctor, MSc.)

Fig. 3

Representative real-time and colour/pulsed Doppler images of placental development at 12 weeks gestation. a) Transverse view of body of uterus outlining the uterine wall (outer line) with an anteriorly located placenta (inner line). b) The same view with colour Doppler (at conventional arterial setting of 38 cm/s). Note flow signals in this range are confined to the myometrium. c) Colour/pulsed Doppler identification of the proximal left uterine artery. Note low-impedance waveform with high (135 cm/s) peak systolic velocity. d) Colour-pulsed Doppler identification of arterial signals in the lateral myometrium, above the left proximal uterine artery. Note low-impedance waveform similar to Fig. 3c but at lower (56 cm/s) velocity. No such signals are observed entering the basal plate of the placenta. Whilst these images suggest intra-myometrial shunting at the end of the first trimester, the extent to which this phenomenon occurs in the second and third trimesters requires further research.

Fig. 4

a) Graphs showing the relationship between the flow volume and the radius of a spiral artery, assuming a length of 1 cm and a pressure drop of 80 mmHg. The upper curves correspond to a viscosity of 3 mPa s and the lower curves to a viscosity of 6 mPa s. b) Graphs showing the relationship between the speed of flow and the radius of a spiral artery, assuming a constant radius and no dilation.

Fig. 5

a) Graphs showing the relationship between speed of flow on exit from the artery (solid lines) and Reynolds number (dashed lines) with the radius of the artery. The upper curves correspond to a viscosity of 3 mPa s and the lower curves to a viscosity of 6 mPa s. Note that the scale for speed is logarithmic, so that dilation leads to a major reduction in exit velocity. b) Graph showing the pressure gradient along the non-dilated and dilated portions of a converted spiral artery.

Fig. 6

Diagrammatic representation (not to scale) of the effects of spiral artery conversion on the inflow of maternal blood into the intervillous space and on lobule architecture predicted by modelling. Dilation of the distal segment in normal pregnancies will reduce the velocity of incoming blood, and the residual momentum will carry the blood into the central cavity (CC) of the lobule, from where it will disperse evenly through the villous tree. Transit time to the uterine vein is estimated to be in the order of 25–30 s, allowing adequate time for oxygen exchange. The pressure of the maternal blood, indicated in mmHg by the figures in blue, will drop across the non-dilated segment of the spiral artery, the dimensions of which are given alongside. In pathological pregnancies, where no or very limited conversion occurs, the maternal blood will enter the intervillous space at speeds of 1–2 m/s. The high Reynolds number predicts turbulent flow, indicated by the circular arrows. We suggest that the high momentum ruptures anchoring villi (asterisked) and displaces others to form echogenic cystic lesions (ECL) lined by thrombus (brown). The transit time will be reduced, so that oxygen exchange is impaired and blood leaves in the uterine vein with a higher oxygen concentration than normal. Trophoblastic microparticulate debris (dotted) may be dislodged from the villous surface, leading to maternal endothelial cell activation. Finally, the retention of smooth muscle cells (SMC) around the spiral artery will increase the risk of spontaneous vasoconstriction and ischaemia–reperfusion injury.