Abstract
Preeclampsia is a severe placenta-related pregnancy disorder that is generally divided into two subtypes named early-onset preeclampsia (onset <34 weeks of gestation), and late-onset preeclampsia (onset ≥34 weeks of gestation), with distinct pathophysiological origins. Both forms of preeclampsia have been associated with maternal systemic inflammation. However, alterations in the placental immune system have been less well characterized. Here, we studied immunological alterations in early- and late-onset preeclampsia placentas using a targeted expression profile approach. RNA was extracted from snap-frozen placenta samples (healthy n=13, early-onset preeclampsia n=13, and late-onset preeclampsia n=6). The expression of 730 immune-related genes from the Pan Cancer Immune Profiling Panel was measured, and the data were analyzed in the advanced analysis module of nSolver software (NanoString Technology). The results showed that early-onset preeclampsia placentas displayed reduced expression of complement, and toll-like receptor (TLR) associated genes, specifically TLR1 and TLR4. Mast cells and M2 macrophages were also decreased in early-onset preeclampsia compared to healthy placentas. The findings were confirmed by an immunohistochemistry approach using 20 healthy, 19 early-onset preeclampsia, and 10 late-onset preeclampsia placentas. We conclude that the placental innate immune system is altered in early-onset preeclampsia compared to uncomplicated pregnancies. The absence of these alterations in late-onset preeclampsia placentas indicates dissimilar immunological profiles. The study revealed distinct pathophysiological processes in early-onset and late-onset preeclampsia placentas and imply that a tailored treatment to each subtype is desirable.
Highlights
Placentation and subsequent development of the placenta are essential processes that determine an uneventful pregnancy and good fetal outcome
Late-onset preeclampsia placentas did not display any immune-related gene expression differences compared to healthy controls after correction for multiple testing (Figure 1B)
Eight downregulated and six upregulated genes were found in late-onset compared to early-onset preeclampsia placentas (Figure 1C)
Summary
Placentation and subsequent development of the placenta are essential processes that determine an uneventful pregnancy and good fetal outcome. Problems of placental development and adaptation can result in impaired fetal growth and preeclampsia affecting 2-8% of all pregnancies [1]. Adaptive immune cells including regulatory T cells and B cells are present in lower numbers and may be involved in maintaining a stable and appropriate immune response during later stages of pregnancy [5, 7, 8]. An increase in the concentrations of maternally circulating endoglin and sFlt, and a subsequent decrease in placental growth factor (PlGF) signaling were identified as the major causal factors for the development of preeclampsia [1, 2]. The involvement of the placental immune system is less clear as studies on placental immune cell alterations in preeclampsia have reported contradictory results, and the exact roles of placental immune cells in preeclampsia remain to be elucidated [5, 6]
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