Genetic factors including inherited predisposing genes and epigenetic inluences.
Discussed in Chapter 5 (p. 88), normal implantation is characterized by extensive remodeling of the spiral arterioles within the decidua basalis (Fig. 40-2). Endovascular trophoblasts replace the vascular endothelial and muscular linings to enlarge the vessel diameter (Zhou, 1997). The veins are invaded only superficially.
In some cases of preeclampsia, however, trophoblastic invasion may be incomplete. With this, decidual vessels, but not myometrial vessels, become lined with endovascular trophoblasts. The deeper myometrial arterioles thus do not lose their endothelial lining and musculoelastic tissue, and their mean external diameter is only half that of corresponding vessels in normal placentas (Fisher, 2015). In general, the magnitude of defective trophoblastic invasion correlates with the severity of the hypertensive disorder (Madazli, 2000). And importantly, it is more prevalent in women with early-onset preeclampsia (Khodzhaeva, 2016). cMahon and associates (2014) found that lower levels of soluble antiangiogenic growth factors may be involved in this faulty endovascular remodeling.
From placental electron microscopy studies, early preeclamptic changes include endothelial damage, insudation of plasma constituents into vessel walls, proliferation of myointimal cells, and medial necrosis (De Wolf, 1980). Hertig (1945) referred to lipid accumulation in myointimal cells and macro phages as atherosis. These indings are more common in placentas from women diagnosed with preeclampsia before 34 weeks (Nelson, 2014b). Acute placental vascular atherosis may also identiy a group of women at greater risk for later atherosclerosis and cardiovascular disease (Staf, 2015). In pregnancy, the abnormally narrow lumen of spiral arterioles likely impairs placental blood flow. Diminished perfusion and a hypoxic environment eventually lead to release of placental debris or microparticles.
At this point, these changes incite a systemic inlammatory response, which is stage 2 of the preeclampsia syndrome (Lee, 2012; Redman, 2012). Defective placentation is posited to further cause the susceptible woman to develop gestational hypertension, the preeclampsia syndrome, preterm delivery, a growth-restricted fetus, and/or placental abruption (Brosens, 2011; Labarrere, 2017; Nelson, 2014b).
IVlaternal immune tolerance to paternally derived placental and fetal antigens is discussed in Chapter 5 (p. 95). Loss of this tolerance is another cited theory for preeclampsia (Erlebacher, 2013). Certainly, the histological changes at the maternalplacental interface are suggestive of acute graft rejection.
Inferential data also suggest that preeclampsia is an immunemediated disorder. For example, the risk of preeclampsia is appreciably enhanced in circumstances in which formation of blocking antibodies to placental antigenic sites might be impaired. In this scenario, the irst pregnancy would carry a higher risk. Tolerance dysregulation might also explain an ele vated risk when the paternal antigenic load is increased, that is, with two sets of paternal chromosomes-a "double dose."