Regulation of Uterine Spiral Artery Remodeling: a Review
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ORIGINAL ARTICLE
Regulation of Uterine Spiral Artery Remodeling: a Review Eugene D. Albrecht 1,2
&
Gerald J. Pepe 3
Received: 11 February 2020 / Accepted: 6 May 2020 # The Author(s) 2020
Abstract Extravillous trophoblast remodeling of the uterine spiral arteries is essential for promoting blood flow to the placenta and fetal development, but little is known about the regulation of this process. A defect in spiral artery remodeling underpins adverse conditions of human pregnancy, notably early-onset preeclampsia and fetal growth restriction, which result in maternal and fetal morbidity and mortality. Many in vitro studies have been conducted to determine the ability of growth and other factors to stimulate trophoblast cells to migrate across a synthetic membrane. Clinical studies have investigated whether the maternal levels of various factors are altered during abnormal human pregnancy. Animal models have been established to assess the ability of various factors to recapitulate the pathophysiological symptoms of preeclampsia. This review analyzes the results of the in vitro, clinical, and animal studies and describes a nonhuman primate experimental paradigm of defective uterine artery remodeling to study the regulation of vessel remodeling. Keywords Uterine artery remodeling . Preeclampsia . Animal models
Introduction During early human pregnancy, extravillous trophoblast (EVT) migrates to, invades, and replaces the vascular smooth muscle cells (VSMC), endothelial cells, and elastic lamina within, thereby remodeling the uterine spiral arteries [1–4]. Consequently, these arteries change from high-resistance/ low-capacity to low-resistance/high-capacity vessels, and thus, uterine artery blood flow increases with advancing gestation to enhance placental perfusion and promote fetal development. Defective uterine artery remodeling (UAR) underpins the etiology of certain pregnancy disorders that comprise the syndrome of placental ischemia [5, 6], notably early-onset preeclampsia, defined as premature delivery prior to week 34
* Eugene D. Albrecht [email protected] 1
Bressler Research Laboratories, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, 655 West Baltimore St., Baltimore, MD, USA
2
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA
3
Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA, USA
of gestation and associated with a high rate of fetal growth restriction [7–13]. The term preeclampsia is used throughout this review to refer to early onset since in contrast to late-onset preeclampsia, i.e., delivery after 34 weeks, it is underpinned by defective UAR. Preeclampsia is associated with maternal systemic vascular endothelial inflammation-activation-dysfunction, hypertension, renal glomerular endotheliosis, and proteinuria, as well as maternal and neonatal morbidity/ mortality [14–20]. It has been proposed that as a consequence of impaired UAR and placental perfusion,
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