Obstet Gynecol Sci.  2013 Jan;56(1):2-7. 10.5468/OGS.2013.56.1.2.

Pathogenesis and promising non-invasive markers for preeclampsia

• Kim YJ

• KMID: 1857179
• DOI: http://doi.org/10.5468/OGS.2013.56.1.2

Abstract

Preeclampsia is one of the leading causes of maternal mortality/morbidity and preterm delivery in the world, affecting 3% to 5% of pregnant women. The pathophysiology of preeclampsia likely involves both maternal and fetal/placental factors. Abnormalities in the development of placental vessels early in pregnancy may result in placental hypoperfusion, hypoxia, or ischemia. Hypoperfusion, hypoxia, and ischemia are critical components in the pathogenesis of preeclampsia because the hypoperfused placenta transfers many factors into maternal vessels that alter maternal endothelial cell function and lead to the systemic symptoms of preeclampsia. There are several hypotheses to explain the pathogenesis of preeclampsia, including altered angiogenic balance, circulating angiogenic factors (such as marinobufagenin, a bufadienolide trigger), and activation of the renin-angiotensin system. Epigenetically-modified cell-free nucleic acids that circulate in plasma and serum might be novel markers with promising non-invasive clinical applications in the diagnosis of preeclampsia.

Keyword

Preeclampsia; Pathogenesis; Angiogenic factors; Marinobufagenin; Cell-free nucleic acids

MeSH Terms

Angiogenesis Inducing Agents
Anoxia
Bufanolides
Endothelial Cells
Female
Humans
Ischemia
Nucleic Acids
Placenta
Plasma
Pre-Eclampsia
Pregnancy
Pregnant Women
Renin-Angiotensin System
Angiogenesis Inducing Agents
Bufanolides
Nucleic Acids

Figure

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  Fig. 1 Abnormal placentation in preeclampsia. In normal pregnancies, extravillous cytotrophoblasts of fetal origin invade the uterine spiral arteries of the decidua and myometrium. These invasive cytotrophoblasts replace the endothelial layer of the maternal spiral arteries, transforming them from small, high-resistance vessels into large-caliber vessels (A). However, in preeclampsia, this transformation is incomplete. Cytotrophoblast invasion of the spiral arteries is limited to the superficial decidua and does not reach the myometrium (B) (From Lam et al. [5], with permission from Wolters Kluwer Health).

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  Fig. 2 (A) Chemical structures of the bufadienolides and the cardenolides. The compounds on the left side are cardenolides and those on the right side are bufadienolides. (B) The chemical structures of marinobufagenin and resibufogenin (From Uddin et al. [17], with permission from Elsevier).

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  Fig. 3 Working model of the role of MBG in preeclampsia pathogenesis and its association with the RAS and oxidative stress (From Uddin et al. [17], with permission from Elsevier). MBG, marinobufagenin; RAS, renin-angiotensin system; RBG, Resibufogenin; sFlt1, soluble fms-like tyrosine kinase 1; sEng, endoglin; VEGF, vascular endothelial growth factor; BP, blood pressure; IUGR, intrauterine growth restriction.

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