Microarray Profiling Reveals That Placental Transcriptomes of Early-onset HELLP Syndrome and Preeclampsia Are Similar

Abstract

Background The involvement of the placenta in the pathogenesis of preeclampsia and HELLP syndrome is well established, and placental lesions also similar in these two syndromes. Here we aimed to examine the placental transcriptome and to identify candidate biomarkers in early-onset preeclampsia and HELLP syndrome. Methods Placental specimens were obtained at C-sections from women with early-onset preeclampsia and HELLP syndrome, and from controls who delivered preterm or at term. After histopathological examination, fresh-frozen placental specimens were used for microarray profiling and validation by qRT-PCR. Differential expression was analysed using log-linear models while adjusting for gestational age. Gene ontology and pathway analyses were used to interpret gene expression changes. Tissue microarrays were constructed from paraffin-embedded placental specimens and immunostained. Results Placental gene expression was gestational age-dependent among preterm and term controls. Out of the 350 differentially expressed genes in preeclampsia and 554 genes in HELLP syndrome, 224 genes (including LEP, CGB, LHB, INHA, SIGLEC6, PAPPA2, TREM1, and FLT1) changed in the same direction (elevated or reduced) in both syndromes. Many of these encode proteins that have been implicated as biomarkers for preeclampsia. Enrichment analyses revealed similar biological processes, cellular compartments and biological pathways enriched in early-onset preeclampsia and HELLP syndrome; however, some processes and pathways (e.g., cytokine-cytokine receptor interaction) were over-represented only in HELLP syndrome. Conclusion High-throughput transcriptional and tissue microarray expression profiling revealed that placental transcriptomes of early-onset preeclampsia and HELLP syndrome largely overlap, underlying a potential common cause and pathophysiologic processes in these syndromes. However, gene expression changes may also suggest a more severe placental pathology and pronounced inflammatory response in HELLP syndrome than in preeclampsia.

Microarray Screening for Novel Preeclampsia Biomarker Candidates

“…Similar to other studies using a microarray RNA expression profile of placental villous tissue of preeclamptic patients, we found differentially expressed genes such as β-hCG [24] or LHB, which could be the result of altered trophoblast physiology [25]. The elevated levels of these molecules, which are predominantly expressed in the syncytiotrophoblast, may be indicative of altered pathways that are related to uteroplacental vascular insufficiency or placental oxidative stress and reoxygenation [26].…”

The Impact of Maternal-Fetal Genetic Conflict Situations on the Pathogenesis of Preeclampsia

“…These genes could have a role in supplying the main source of metabolic energy during each pregnancy stage. The metabolism-related genes in preeclampsia may be associated with parental alleles that influence maternal investment in fetus (Millar et al 2005;Zhou et al 2006;Laivuori 2007;Founds et al 2009;Johansson et al 2011;Løset et al 2011;Rajakumar et al 2011;Sado et al 2011;Tsai et al 2011;Uusküla et al 2011;Várkonyi et al 2011;Jia et al 2012;Lapaire et al 2012;Iglesias-Platas et al 2013). As shown in Table 1, a majority of genes, including PAPPA2 (pappalysin 2), ERO1L (endoplasmic reticulum oxidoreductin-1-like), SASH1 (SAM and SH3 domain containing 1), HTRA1 (HtrA serine peptidase 1), INSL4 (insulin-like 4), and TRIP10 (thyroid hormone receptor interactor 10), function as regulators of insulin and IGF bioavailability and then energy metabolism in the fetus.…”

Placental transcriptome in development and pathology: expression, function, and methods of analysis

“…[82][83][84][85][86][87][88][89] Additionally, very similar changes in placental gene expression have been noted to occur in HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome by microarray analysis. 90 Meta and integrative analysis of mRNA microarray data in PE While each published data set of PE placentas is relatively small (1-23 PE patients), when combined they represent nearly 250 PE samples. Interestingly, simultaneous assessment of multiple microarray data sets is possible, but has important considerations and limitations.…”