Abstract P177: Reduced Expression of Regulator of G-Protein Signaling-2 (RGS2) in the Placenta During Preeclampsia

Abstract

Preeclampsia (PE) is a serious cardiovascular condition of late pregnancy. Genetic risk factors and the early-gestational etiology remain largely unclear, though evidence supports excessive activation of Gαq signaling within the placenta in response to various hormones including vasopressin, endothelin, and angiotensin. Regulator of G-protein Signaling 2 (RGS2) acts as an endogenous terminator of Gαq signaling, and previous association studies have identified an increased risk for PE and its sequelae in women carrying a single nucleotide polymorphism that is expected to reduce levels of RGS2. We hypothesized that RGS2 is expressed in placental trophoblasts, and that reduced expression of RGS2 in placental tissue may represent a risk factor for the development of PE. Whole placenta samples and clinical data from preeclamptic and clinically-matched control pregnancies were obtained from the University of Iowa Maternal-Fetal Tissue Bank (IRB#200910784) and examined for mRNA levels of the B/R4 family of RGS proteins, including RGS2. Of the members examined (RGS2, -3, -4.2, -4.3, -4.4, -4.5, and -5) in control placentas (n=9), only RGS2 (Ct 28.8±0.7 vs 18S Ct 12.1±0.4) and RGS4.3 (Ct 23.0±0.4 vs 18S Ct 13.3±0.3) transcripts were expressed above background levels. RGS2 protein expression was then confirmed in human placental tissues by Western blot. RGS2 mRNA expression was 3-fold higher in fetal (amniotic, p<0.05) layers than maternal (decidual) layers. In preeclamptic placenta (n=11), RGS2 may be suppressed (1.0±0.4 vs 0.2±0.3-fold, p=0.1) while RGS4.3 remains unchanged (1.0±0.4 vs 1.1±0.4 fold, p=0.8). Initial immunohistochemical detection confirms cytoplasmic localization of RGS2 in trophoblasts of wildtype mouse placenta, despite exclusive nuclear localization in other tissues. We conclude that human placenta expresses RGS2, and that this expression may be suppressed during preeclampsia. Loss of RGS2 expression may result in disinhibited trophoblast Gαq signaling, and ultimately placental insufficiency.