Mechanisms of Uterine Artery Dysfunction in Pregnancy Complications

Abstract

Pregnancy is a unique condition, and the vascular processes that are required for this undertaking are both complex and extensive. In this review, we discuss the vascular adaptations which occur in the maternal uterine arterial bed to maintain blood supply to the fetal-placental unit. In complicated pregnancies, inadequate remodeling of the uterine arteries, hormonal imbalances, and pre-existing conditions such as obesity, hypertension, diabetes etc. may lead to maladaptations of the uterine vasculature that includes increased vasoconstriction and endothelial dysfunction. Ultimately, uterine artery dysfunction results in increased vascular resistance impeding blood flow to the fetal-placental unit and limiting fetal growth and development. A strong association exists between poor fetal development in utero and later life health issues, which can include obesity, poor neurological development, and enhanced susceptibility to cardiovascular disease. Therefore, the detrimental outcomes of a complicated pregnancy are far-reaching and significantly impact the health of the population as a whole. Many treatment options to improve maternal uterine artery function and ameliorate the impact on the fetus are being considered. A particular difficulty in treating complicated pregnancies is the presence of not 1 but (at least) 2 patients. Novel approaches are required to successfully improve pregnancy outcomes and minimize the impact on later life health.

Plasticity of the Maternal Vasculature During Pregnancy

“…For example, sFlt-1 [a soluble VEGF (vascular endothelial growth factor) receptor] and endoglin (a soluble receptor for TGF-β) are both upregulated in preeclampsia, and their circulating levels are positively correlated with disease severity. By binding important signaling molecules and preventing their access to tissues, soluble receptors like sFlt-1 and endoglin prevent normal adaptation and lead to maternal endothelial dysfunction, which is a hallmark of this human disease that is characterized by new-onset hypertension and proteinuria (10, 11).…”

Maternal Vascular Physiology in Preeclampsia

“…Mechanisms underlying changes in calcium concentrations involve transient receptor potential vanilloid type 3 and type 4 ion channels, upregulation of transient receptor potential canonical type 3, and upregulation of connexins. 5,113 Studies on Ca 2+ entry mechanisms are relatively new and need to be expanded in models of experimental preeclampsia to better understand the pathophysiology of the uteroplacental circulation.…”

Intermittent hypoxia impairs uterine artery function in pregnant mice

“…The remodelling process involves natural killer cells, trophoblast invasion into the vascular wall and apoptosis of smooth muscle cells (Morton et al . ). This remodelling process reduces total vascular resistance in the mouse uterine bed by 47% (Rennie et al .…”

“…The uteroplacental circulation undergoes continuous remodelling throughout pregnancy including: (i) increased diameter of uterine arteries, (ii) vasculo/angiogenesis, and (iii) remodelling of spiral arteries (Morton et al . ). These changes ensure adequate oxygen and nutrient supply to the fetus.…”