European Journal of Obstetrics & Gynecology and Reproductive Biology
Structure adaptation and blood flow control in the uterine arterial system after hemochorial placentation
Introduction
Maternal blood flow is the limiting factor of placental oxygen delivery. In this paper, the adjustment of oxygen delivery and of maternal placental flow by the uterine arterial system is described for the hemochorial placenta where foetal placental capillaries are exposed to maternal placental blood pressure. We first review that the trophoblast cells build a highly conductive hemochorial stream bed for maternal blood in the placenta which allows placental blood perfusion at low pressure. We describe how the maternal vessels structurally adapt and provide adequate blood flow at low intraplacental pressure. After discussing the present concepts for the control of arterial adaptation and placental blood flow, a somehow provocative concept is presented: it is hypothesized that the trophoblast cells, by forming the highly conductive hemochorial stream bed, trigger and control arterial remodeling and blood flow rate simply by building up shear stress which is known to be the basic signal everywhere for structural vascular adjustment to growth. The concept has been discarded previously in view of seemingly low shear stress in the over-dilated peripheral placental arteries studied on the exteriorized mesometrium. There is however some evidence now that the low peripheral shear stress in these dilated arteries is an artifact. In reality, the arteries seem to be compressed by the surrounding pressure and undergo particular high shear stress. So, the concept of shear stress mediated control of arterial adaptation and blood flow is represented.
Section snippets
In the course of hemochorial placentation, trophoblast cells build a highly conductive streambed for maternal blood, which allows for adequate maternal blood flow at low placental blood pressure
In Fig. 1, the maternal placental vascular bed of the hemochorial labyrinthine guinea pig placenta is shown. Maternal blood flows in channels built by the trophoblast syncytium. The channels are wide and obviously of high conductance. The foetal placental capillaries are located in the wall of the maternal streambed, directly exposed to the pressure of the maternal blood. The maternal vascular bed in the guinea pig placenta is described extensively in [16]. The wide and obviously highly
In the course of hemochorial placentation, controlled remodeling occurs in the maternal vessels (the physiological changes), providing maternal placental blood supply at a rate adequate for maternal–foetal exchange as well as for the required low intraplacental pressure
The Carnegie collection of human conceptus of various stages of gestation shows the early stages of the development of the placental vascular bed of the placenta. The figures show the lacunar channels filled with blood and connections with maternal endometrial capillaries ([4], [10], for discussion see [32]). The adjustment of the highly conductive lacunar system to the endometrial microsvascular system is expected to increase dramatically local regional blood flow and shear stress in the
The proximal portions of the uterine arterial system display restricted adaptation maintaining arterial flow resistance high compared to placental resistance
More proximal sections of the casts of the uterine arterial system appear narrower than the distal ones (see Fig. 3). During gestation, they dilate and elongate at a modest, seemingly controlled way, maintaining flow resistance to some extent. In guinea pigs, the external diameter of the segmental arteries arising from the uterine arcade increase two-fold during pregnancy, from around 200 to around 400 μm (unpublished observations). Similar changes were found in the rat, where the uterine artery
The peripheral and final portions of the uterine arterial system show over-dilatation and degenerative wall changes
The peripheral portions of the maternal arteries show more increase in circumference than more centrally located ones. It may be recalled that there are interspecies differences; the over-dilatation of the more peripheral parts of the arterial system is also seen in man and rhesus monkeys, but not in mice and rats. In guinea pigs especially dramatic growth processes in the final arterial parts occur, circumference increases three-fold, mass increases 50-fold, DNA 30-fold [26]. Massive changes
The final parts of the uterine arterial system seem to collapse in pregnancy
The final parts of the uterine arteries in guinea pigs (the branches of the segmental arteries and the arcuate arteries) have, when inspected on the exteriorised mesometrium of anaesthetized animals, a circular cross-sectional area. However, a 6 mm agar layer is able to partially compress the final portions of the segmental arteries (unpublished observations). In guinea pig killed and fixed in situ, the peripheral segmental arteries were found to be flattened tubes looking as they were
Uterine arterial system of the hemochorial placenta versus the uterine arterial system of an epitheliochorial placenta
In sheep, along the accessible arteries outside the uterus there is no appreciable blood pressure fall. Blood pressure in the large and medium sized arteries of sheep is maintained, no end-arterial low-pressure occurs [22]. Placental flow rate in epitheliochorial placentas is about twice that in hemochorial placentas (for review see [20]) as mentioned above. There no need to protect foetal placental capillaries from maternal placental blood flow rate and pressure.
Humoral factors, invading trophoblast cells and hemodynamic forces (shear stress) are assumed to be triggers of physiological changes. The trophoblast invasion concept is generally accepted but still questionable since physiological changes occur also before and outside the region of invasion
According to the humoral concept, trophoblast factors are liberated by the placenta and reach the vessel walls. They trigger and maintain arterial remodeling, adjusting this way arterial conductance and oxygen supply. Inspection of the in situ anatomy of the vessels supplying the placenta in guinea pigs, shows arteries and veins in close neighborhood, surrounded by the perimetrium over a longer distance, suggesting that trophoblast factors such as oestrogen, delivered in the maternal venous
Definition and parameters of shear stress—ways and consequences of shear stress control
Some basic statements on shear stress shall be allowed: shear stress τ is the force per endothelial surface acting in the direction of flow (see Fig. 5), deforming endothelial cells length wise the direction of flow. The force is given by the blood pressure difference ΔP times cross-sectional area, the endothelial surface by the circumference times length; shear stress τ in a round vessel, therefore, is proportional to the pressure drop ΔP times the ratio of diameter D over length l:
The physiological changes on the uterine arterial system during gestation are likely to be caused by shear stress resulting from the formation of the highly conductive hemochorial streambed
Even for the physiological changes in pregnancy, shear stress is a likely inducer and controller on the following reasons: (1) shear stress is present in the uterine arterial system during pregnancy. After formation of the highly conductive hemochorial stream bed, the endarterial pressure falls to values below 20 mmHg. Shear stress is likely to be present even in the over-dilated parts of the segmental arteries because of endarterial collapse as described above. Expression of endothelial NO
Speculations on symptoms and pathogenesis of preeclampsia
In pregnancy-induced hypertension (preeclampsia), preplacental arteries show round diameters without over-dilatation and wall damage; trophoblast cell invasion is shortened. The placenta shows infarcted areas where also fetal capillary flow is absent [6]. The shear stress concept of gestational uterine arterial adaptation may provide some understanding of the coincidence of the various phenomena: central hypertension should be associated also with increased uterine endarterial pressure and
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