Maternal Uterine Vascular Remodeling During Pregnancy

Abstract

Remodeling of the maternal uterine vasculature during pregnancy is a unique cardiovascular process that occurs in the adult and results in significant structural and functional changes in large and small arteries and veins, and in the creation of the placenta--a new fetomaternal vascular organ. This expansive, hypertrophic process results in increases in both lumen circumference and length, and is effected through a combination of tissue and cellular hypertrophy, endothelial and vascular smooth muscle hyperplasia, and matrix remodeling. This review summarizes what is currently known about the time course and extent of the remodeling process, and how local vs. systemic factors influence its genesis. The main focus is on upstream maternal vessels rather than spiral artery changes, although the latter are considered from the overall hemodynamic perspective. We also consider some of the underlying mechanisms and provide a hypothetical scenario that integrates our current knowledge. Abrogation of this adaptive vascular process is associated with several human gestational pathologies such as preeclampsia and intrauterine growth restriction (IUGR), which not only raise the risk of infant mortality and morbidity but are also a significant source of maternal mortality and susceptibility to cardiovascular and other diseases for both mother and neonate later in life.

Enhanced Uterine Artery Stiffness in Aged Pregnant Relaxin Mutant Mice Is Reversed with Exogenous Relaxin Treatment1

“…Maximum remodeling of the main uterine artery occurs during late pregnancy and is associated with VSMC hypertrophy and hyperplasia [7][8][9][10]. This remodeling coincides with changes in the biomechanical properties of the artery, with arterial compliance changing as pregnancy advances [2]. Although there are considerable species differences, these biomechanical changes are attributed to alterations in the composition of the uterine artery wall.…”

“…The factors responsible for the remodeling of the uterine vasculature during pregnancy, particularly the main uterine artery, are influenced by a combination of local and systemic pregnancy-dependent factors [2,15]. Studies using pseudopregnant mice demonstrated that the conceptus is not involved in the initial remodeling response of the uterine artery [11], but as pregnancy progresses, the fetoplacental unit plays a major role in mediating expansion of the uteroplacental vasculature [16,17].…”

“…This is achieved through a profound decrease in uterine vascular resistance and structural remodeling of the uterine artery wall [1,2]. Failure of these changes to occur reduces uteroplacental perfusion and contributes to pregnancy complications such as gestational hypertension and intrauterine growth restriction [3][4][5].…”

Long-term under-masculinization in male rabbits due to maternal stress is reversed by prenatal administration of testosterone

“…Rabbits are often used as experimental subjects in studies of prenatal effects on prenatal development because they are polytocous and they have hemochorial placentation (as in rat, house mouse and humans) (Faber and Hart, 1967;Flexner and Pohl, 1941;Osol and Mandala, 2009). Although, effects of prenatal T administration have been established in female rabbits (Bánszegi et al, 2009(Bánszegi et al, , 2010, no studies have been made on the effect of prenatal T administration on males.…”

Mechanism of hydralazine-induced relaxation in resistance arteries during pregnancy

“…It is well known that pregnancy causes changes in systemic and uterine vessel reactivity and function through changes in both the endothelium and vascular smooth muscle cells [19][20][21][22]. It is therefore important to understand the mechanism by which hydralazine induces vasodilation during pregnancy.…”