Tumor suppressor and growth regulatory genes are overexpressed in severe early‐onset preeclampsia – an array study on case‐specific human preeclamptic placental tissue

Abstract

It is concluded that up-regulation of tumor suppressor and growth regulatory genes may play an important role in the pathogenesis of severe early-onset preeclampsia.

Relationship between Maternal Immunological Response during Pregnancy and Onset of Preeclampsia

“…These include transforming growth factor-beta (TGF- β ), whose participation in immunoregulation and angiogenesis has been well-established, and angiogenic factors placenta growth factor (PIGF), and vascular endothelial growth factor (VEGF). Conversely in preeclampsia, when KIR-AA of maternal uNK cells recognize the HLA-C of the extravillous trophoblast, uNK cells display a poorer expression of these mediators [3], as well as an overexpression of antiangiogenic factors like soluble endoglin (sENG) and soluble fms-like tyrosine (sFLT1) kinase-1 factor. sENG inhibits TGF- β 1 from binding to the surface of its receptors and diminishes nitric oxide-mediated endothelial signaling.…”

“…Preeclamptic women do not show significantly different serum levels of RANTES, a cytokine produced by uNK cells at the human fetal-maternal interface, if compared with healthy pregnant women [34]. Nevertheless, the placental gene expression of RANTES has been found to be upregulated in severe early onset preeclampsia from gestational weeks 25 to 27 when compared with placental samples of uncomplicated pregnancies in similar gestational weeks [3]. Further studies are required to elucidate the exact contribution of RANTES in inducing a tolerogenic maternal immune response to allow for trophoblast survival, migration, and invasion.…”

“…Although the precise etiology of the disorder is still unknown, deficient early placentation is particularly associated with early onset preeclampsia [2]. In fact, abnormal placentation is thought to be immunologically mediated [2, 3]. As prevention and prediction of preeclampsia are still not possible, symptomatic clinical management should focus on preventing maternal morbidity (e.g., generalised seizures of eclampsia) and mortality [2].…”

“…Compared to pregnancy by autologous in vitro fertilization (IVF), the prevalence of hypertensive complications is 26–37% as opposed to 8%, with an odds ratio (OR) of 7.1 for the ED group [4]. Furthermore, the incidence of pregnancy-induced hypertension is higher in ED-pregnant women, who are not related to the donor and have not been previously exposed to the donor's sperm [3–5]. …”

DNA methylation in the human placenta and fetal growth (Review)

“…Alterations in the expression of tumour suppressor gene expression profiles have been identified in placentas from preeclamptic pregnancies (68). A distinct pattern of tumour-associated methylation, linking a coordinated series of epigenetic silencing events, similar to those associated with some tumours, in the distinct, features of normal human placental invasion and function has been observed (69).…”