Localization and quantification of HDAC9 and RGS2 expression in placenta during preeclampsia.

Preeclampsia is a multifaceted pregnancy-associated hypertensive disorder that poses a major threat to maternal and fetal health. Though the etiology is not fully understood, syncytiotrophoblast stress is postulated to be a major driver of maternal symptomology. We previously demonstrated that Regulator of G protein Signaling-2 (RGS2) expression is decreased in human preeclamptic placenta and has a transcriptional dependence on histone deacetylase 9 (HDAC9) in trophoblast cells. Further, experimental reductions of Rgs2 expression in the mouse fetoplacental unit are sufficient to induce preeclampsia-like features, including placental stress, in C57BL/6J dams. Here we examined the hypotheses that HDAC9 and RGS2 are both expressed within syncytiotrophoblasts, that HDAC9 and RGS2 expression are positively correlated within these cells, and that expression of each is reduced within syncytiotrophoblasts during preeclampsia. HDAC9 and RGS2 mRNA were localized and quantified in syncytiotrophoblast cells of human placental samples from pregnancies with and without preeclampsia, using laser-capture microdissection and in situ hybridization methods. Expression of Hdac9 and Rgs2 were similarly localized in the syncytiotrophoblast of mouse placenta. Throughout, HDAC9/Hdac9 and RGS2/Rgs2 were detected and positively correlated in syncytiotrophoblasts, but expression of each was substantially reduced during preeclampsia. These results document reduced HDAC9 and RGS2 expression specifically in syncytiotrophoblast cells during preeclampsia and provide additional correlative support of HDAC9-mediated control of RGS2 expression within this population of trophoblasts. This work provides rationale to further explore cell-specific disruptions in HDAC9 and RGS2 control and function as a cause of syncytiotrophoblast stress and ultimately preeclampsia.