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 3 m/s in the non-dilated part of an artery of 0.4–0.5 mm diameter to approximately 10 cm/s at the 2.5 mm diameter mouth, depending on the exact radius and viscosity. This rate predicts a transit time through the intervillous space of approximately 25 s, 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 1–2 m/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.
The purpose of this study was to establish the time course and hemodynamic significance of de novo formed and enlarged uteroplacental arteries during pregnancy. Using x-ray microcomputed tomography ...(n = 4–7 placentas from 2–4 dams/gestational group), uteroplacental arterial vascular dimensions were measured at individual implantation sites. Dimensions and topology were used to compute total and vessel-specific resistances and cross-sectional areas. Diameter enlargement of the uterine artery (+55% by Embryonic Day 5.5 E5.5) and preplacental radial arteries (+30% by E8.5) was significant only in early gestation. Formation of spiral arteries (E9.5–E11.5), maternal canals, and canal branches (E11.5–E13.5) during midgestation was followed by enlargement of these vessels such that, from E9.5 to E17.5 (near term), spiral artery resistance dropped 9-fold, and canal resistance became negligible. A 12-fold increase in terminal vessel cross-sectional area was nearly sufficient to offset known increases in flow so that blood velocity entering the exchange region was predicted to increase by only 2-fold. The calculated 47% decrease in total resistance downstream of the uterine artery, determined from vascular geometry, was in accord with prior uterine blood flow data in vivo and was due to enlarging spiral artery diameters. Interestingly, radial artery resistance was unchanged after E9.5 so that radial arteries accounted for 91% of resistance and pressure drop in the uteroplacental arterial network by E17.5. These findings led us to propose functional roles for the three morphologically defined vessel types: radial arteries to reduce pressure, spiral artery enlargement to increase flow with gestation, and maternal canal elaboration and enlargement to maintain low exit velocities into the exchange region.
Uteroplacental blood flow increases as pregnancy advances. Adequate supply of nutrients and oxygen carried by uteroplacental blood flow is essential for the well-being of the mother and ...growth/development of the fetus. The uteroplacental hemodynamic change is accomplished primarily through uterine vascular adaptation, involving hormonal regulation of myogenic tone, vasoreactivity, release of vasoactive factors and others, in addition to the remodeling of spiral arteries. In preeclampsia, hormonal and angiogenic imbalance, proinflammatory cytokines and autoantibodies cause dysfunction of both endothelium and vascular smooth muscle cells of the uteroplacental vasculature. Consequently, the vascular dysfunction leads to increased vascular resistance and reduced blood flow in the uteroplacental circulation. In this article, the (mal)adaptation of uteroplacental vascular function in normal pregnancy and preeclampsia and underlying mechanisms are reviewed.
Adequate uteroplacental blood supply is essential for the development and growth of the placenta and fetus during pregnancy. Aberrant uteroplacental perfusion is associated with pregnancy ...complications such as preeclampsia, fetal growth restriction (FGR), and gestational diabetes. The regulation of uteroplacental blood flow is thus vital to the well-being of the mother and fetus. Ca2+-activated K+ (KCa) channels of small, intermediate, and large conductance participate in setting and regulating the resting membrane potential of vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) and play a critical role in controlling vascular tone and blood pressure. KCa channels are important mediators of estrogen/pregnancy-induced adaptive changes in the uteroplacental circulation. Activation of the channels hyperpolarizes uteroplacental VSMCs/ECs, leading to attenuated vascular tone, blunted vasopressor responses, and increased uteroplacental blood flow. However, the regulation of uteroplacental vascular function by KCa channels is compromised in pregnancy complications. This review intends to provide a comprehensive overview of roles of KCa channels in the regulation of the uteroplacental circulation under physiological and pathophysiological conditions.
The purpose of this study was to establish the time course and hemodynamic significance of de novo formed and enlarged uteroplacental arteries during pregnancy. Using x-ray microcomputed tomography ...(n = 4-7 placentas from 2-4 dams/gestational group), uteroplacental arterial vascular dimensions were measured at individual implantation sites. Dimensions and topology were used to compute total and vessel-specific resistances and cross-sectional areas. Diameter enlargement of the uterine artery (+55% by Embryonic Day 5.5 E5.5) and preplacental radial arteries (+30% by E8.5) was significant only in early gestation. Formation of spiral arteries (E9.5-E11.5), maternal canals, and canal branches (E11.5-E13.5) during midgestation was followed by enlargement of these vessels such that, from E9.5 to E17.5 (near term), spiral artery resistance dropped 9-fold, and canal resistance became negligible. A 12-fold increase in terminal vessel cross-sectional area was nearly sufficient to offset known increases in flow so that blood velocity entering the exchange region was predicted to increase by only 2-fold. The calculated 47% decrease in total resistance downstream of the uterine artery, determined from vascular geometry, was in accord with prior uterine blood flow data in vivo and was due to enlarging spiral artery diameters. Interestingly, radial artery resistance was unchanged after E9.5 so that radial arteries accounted for 91% of resistance and pressure drop in the uteroplacental arterial network by E17.5. These findings led us to propose functional roles for the three morphologically defined vessel types: radial arteries to reduce pressure, spiral artery enlargement to increase flow with gestation, and maternal canal elaboration and enlargement to maintain low exit velocities into the exchange region.
Throughout the course of pregnancy, small maternal spiral arteries that are in contact with fetal tissue undergo structural remodeling, lose smooth muscle cells, and become less responsive to ...vasoconstrictors. Additionally, placental extravillous trophoblasts invade the maternal decidua to establish an interaction between the fetal placental villi with the maternal blood supply. When successful, this process enables the transport of oxygen, nutrients, and signaling molecules but an insufficiency leads to placental ischemia. In response, the placenta releases vasoactive factors that enter the maternal circulation and promote maternal cardiorenal dysfunction, a hallmark of preeclampsia (PE), the leading cause of maternal and fetal death. An underexplored mechanism in the development of PE is the impact of membrane-initiated estrogen signaling via the G protein-coupled estrogen receptor (GPER). Recent evidence indicates that GPER activation is associated with normal trophoblast invasion, placental angiogenesis/hypoxia, and regulation of uteroplacental vasodilation, and these mechanisms could explain part of the estrogen-induced control of uterine remodeling and placental development in pregnancy.
Although the relevance of GPER in PE remains speculative, this review provides a summary of our current understanding on how GPER stimulation regulates some of the features of normal pregnancy and a potential link between its signaling network and uteroplacental dysfunction in PE. Synthesis of this information will facilitate the development of innovative treatment options.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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