Profiling the pregnancy-specific glycoprotein genes in pre-eclampsia.

Abstract

Background: Pre-eclampsia (PE) is a hypertensive disorder of pregnancy which is characterised by reduced placental cell invasion into the maternal arteries. Lack of invasion causes insufficient transformation of arteries which disrupts blood flow to the fetus. PE is a leading cause of maternal and fetal death, yet the pathogenesis is not fully elucidated. PE establishes in the early stages of pregnancy but is only diagnosed after 20 weeks gestation due to late onset of symptoms, making early prediction and prevention difficult. Recently, the pregnancy-specific glycoprotein (PSG) genes were proposed as a potential biomarker for early detection of PE and have been hypothesised to have roles in facilitating invasion.

This study aimed to determine if PSG gene expression is downregulated in the PE placenta. Further, expression of PSG genes in first trimester was interrogated to address the role of PSG genes in invasion.

Methods: The NanoString, nCounter platform quantified PSG4, PSG9 and PSG11 gene expression in PE placentae, control (term) placentae (>36 weeks gestation), and first trimester placentae (<13 weeks gestation). The promoter regions of the PSG genes were interrogated using targeted bisulfite sequencing (TBS) on the iSeq platform to quantify DNA methylation.

Main findings: A lower mean expression for each PSG gene was observed in the PE placenta compared to term but this was not statistically significant. PSG9 and PSG11 were significantly upregulated in the invasive period of first trimester compared to term. Supporting these findings, it was confirmed that PSG genes were aberrantly expressed in invasive melanoma cell lines compared to somatic tissues. However, DNA methylation at the promoter of the PSG genes did not inversely correlate with gene expression.

Conclusion: PSG genes may not be implicated in the pathogenesis of PE. However, PSG genes are upregulated in first trimester which may provide insight into how these genes contribute to early placental development. These findings provide further scope to investigate the role of PSG genes in invasion.