Preeclampsia: The Relationship between Uterine Artery Blood Flow and Trophoblast Function

Abstract

Maternal uterine artery blood flow is critical to maintaining the intrauterine environment, permitting normal placental function, and supporting fetal growth. It has long been believed that inadequate transformation of the maternal uterine vasculature is a consequence of primary defective trophoblast invasion and leads to the development of preeclampsia. That early pregnancy maternal uterine artery perfusion is strongly associated with placental cellular function and behaviour has always been interpreted in this context. Consistently observed changes in pre-conceptual maternal and uterine artery blood flow, abdominal pregnancy implantation, and late pregnancy have been challenging this concept, and suggest that abnormal placental perfusion may result in trophoblast impairment, rather than the other way round. This review focuses on evidence that maternal cardiovascular function plays a significant role in the pathophysiology of preeclampsia.

Keywords: maternal cardiovascular system; preeclampsia; uterine artery.

Figure 1

Apoptosis of first-trimester placental endothelial cells (PEC) from normal (normal RI) and high-resistance (high-RI) pregnancies in response to stimulation with TNFα and actinomycin D. First-trimester PEC were cultured with 30 ng/mL TNFα and 800 ng/mL actinomycin D. Images were taken every 15 min over 15 h. (a) The kinetics of the induction of apoptosis for PEC, high RI (n = 8 mean ± SEM, black symbols) and normal RI (n = 8 mean ± SEM, grey symbols). (b) In a separate cohort, normal-RI PEC were incubated with TNFα and actinomycin D alone (n = 4), as well as in the presence of the broad-spectrum caspase inhibitor, zVAD-fmk (n = 4). The results are expressed as mean ± SEM and * p < 0.05. Adapted with permission from Charolidi et al. [9].

Figure 2

Relationship between uterine artery perfusion and cellular function. There are strong associations between maternal uterine artery perfusion and placental cellular function and behaviour. High-resistance Doppler indices (poor placental perfusion) is related to abnormalities of cell motility, penetration, and cell–cell interaction, as well as increased rates of oxidative stress, inflammation, cellular injury, and apoptosis. Adapted with permission from Cartwright et al. [23].

Figure 3

Left ventricle remodelling caused by pregnancy and preeclampsia. Alteration in (volume and pressure) loading conditions and the interaction with mechanical and neurohormonal factors results in ventricular remodeling. At an organ level, remodeling refers to changes in ventricular geometry, volume, and mass. Although remodelling is compensatory in certain pressure and volume overload conditions, progressive ventricular remodeling is ultimately a maladaptive process, contributing to the progression of symptomatic heart failure and an adverse outcome.

Figure 4

Interaction between maternal cardiovascular function and placental function, maternal health, and fetal well-being. Placental oxidative stress or hypoxia is related to the relative balance of cardiovascular functional reserve and the cardiovascular volume/resistance load of pregnancy. The final common pathway that results in the signs and symptoms of preeclampsia involves the release of placental vasoactive substances. Adapted with permission from Thilaganathan and Kalafat. Hypertension. 2019;73:522–531 [68].