PhD Scientific Days 2022

Budapest, 6-7 July 2022

Molecular Sciences I. (Poster discussion will take place in the Aula during the Coffee Break)

A new perspective on Preeclampsia: the potential role of PIWI-piRNA system in placenta development

Luca Gál1, Ábel Fóthi1, Nándor Gábor Than2, Tamás I. Orbán1

1 Transposons and regulatory RNAs Laboratory, Gene Regulation Research Group, Research Centre for Natural Sciences, Budapest
2 Systems Biology of Reproduction Research Group, Research Centre for Natural Sciences, Budapest

Text of the abstract

Preeclampsia (PE) is a pregnancy related multisystemic syndrome, characterized by hypertension and proteinuria after the 20th week of the pregnancy. PE shows wide heterogeneity in severity and time of onset during gestation. Early onset PE, which appears before the 34th week of the pregnancy, is caused by inefficient placenta development and commonly combined with intrauterine growth restriction (IUGR) of the fetus and other severe symptoms of the mother. Late onset PE, however, is caused by chronic underlying diseases of the mother. The RNA-interference based PIWI-piRNA system plays a key role in reproduction and fertility of mice, but its role in human reproduction remains unclear. The short piRNAs are loaded into effector PIWIL proteins to form regulatory complexes, which can recognize their target mRNAs by base pairing and regulate them in transcriptional and post-transcriptional levels.

We aimed to investigate the role of the PIWI-piRNA pathway in PE and develop a non-invasive small-RNA based biomarker system to recognize PE combined with IUGR before the development of symptoms.

We created a high-throughput exosomal small RNA sequencing based method using maternal plasma samples from 5 healthy and 5 PE+IUGR pregnancies to find differences in small RNA expression. Moreover, we compared the mRNA expression levels of PIWIL proteins by qPCR in case of placenta samples from PE and normal pregnancies.

Bioinformatic analysis of the raw sequencing data detected two peaks in the size of the reads, at 21-22nt and 30-35nt, indicating that the two most abundant small RNA subtypes are miRNAs and piRNAs in our samples. We found hsa-piR-016658 as the most abundant piRNA and hsa-miR-486-5p as a most abundant miRNA in our samples which are the most characteristic miRNA and piRNA in plasma samples according to literature. Moreover, we show consistent changes of placental PIWIL expression in case of early and late onset PE compared to healthy condition.

We are at the beginning of biomarker development for early detection of PE+IUGR which requires further analysis of differentially expressed small RNAs in our data and validating our findings in additional samples by qPCR.

This project is implemented within the Cooperative Doctoral Programme and supported by NKFIH and ITM (Research Project Code: C1012947).