Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology

Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):E8468-E8477. doi: 10.1073/pnas.1706546114. Epub 2017 Sep 18.


In preeclampsia (PE), cytotrophoblast (CTB) invasion of the uterus and spiral arteries is often shallow. Thus, the placenta's role has been a focus. In this study, we tested the hypothesis that decidual defects are an important determinant of the placental phenotype. We isolated human endometrial stromal cells from nonpregnant donors with a previous pregnancy that was complicated by severe PE (sPE). Compared with control cells, they failed to decidualize in vitro as demonstrated by morphological criteria and the analysis of stage-specific antigens (i.e., IGFBP1, PRL). These results were bolstered by global transcriptional profiling data that showed they were transcriptionally inert. Additionally, we used laser microdissection to isolate the decidua from tissue sections of the maternal-fetal interface in sPE. Global transcriptional profiling revealed defects in gene expression. Also, decidual cells from patients with sPE, which dedifferentiated in vitro, failed to redecidualize in culture. Conditioned medium from these cells failed to support CTB invasion. To mimic aspects of the uterine environment in normal pregnancy, we added PRL and IGFBP1, which enhanced invasion. These data suggested that failed decidualization is an important contributor to down-regulated CTB invasion in sPE. Future studies will be aimed at determining whether this discovery has translational potential with regard to assessing a woman's risk of developing this pregnancy complication.

Keywords: cytotrophoblast; decidua; human endometrial stromal cells; preeclampsia; transcriptomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Decidua / metabolism
  • Decidua / pathology*
  • Embryo Implantation
  • Endometrium / metabolism
  • Endometrium / pathology*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Pre-Eclampsia / etiology*
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Pregnancy Trimester, First
  • Stromal Cells / metabolism
  • Stromal Cells / pathology*
  • Trophoblasts / metabolism
  • Trophoblasts / pathology*