RNA-Seq Analysis of Chorionic Villi from Recurrent Pregnancy Loss Cases Compared to Normal Early Pregnancy - WCRPL2017 – 2nd World Congress on Recurrent Pregnancy Loss, 19-22, January 2017, Cannes, France

Siim Sõber ¹ Kristiina Rull ^1,3,4 Mario Reiman ¹ Piret Ilisson ⁵ Pirkko Mattila ^6,7 Maris Laan ^1,2

¹Institute of Molecular and Cell Biology, University of Tartu, Estonia
²Institute of Biomedicine and Translational Medicine, University of Tartu, Estonia
³Department of Obstetrics and Gynaecology, University of Tartu, Estonia
⁴Women's Clinic, Tartu University Hospital, Estonia
⁵Department of Genetics, United Laboratories, Tartu University Hospital, Estonia
⁶Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland
⁷Blood Service, Finnish Red Cross, Finland

Background: There are limited studies investigating transcriptome-wide gene expression signatures linked to the disturbances at the maternal-fetal interface, possibly contributing to abnormal placental development and/or reflecting the biological mechanisms behind recurrent pregnancy loss (RPL).

Objective: The study aimed at profiling the transcriptomes and miRNomes of 1^st trimester placental chorionic villi from RPL cases compared to uncomplicated, but electively terminated pregnancies (ETP).

Methods: Study material consisted of 2 RPL cases (≥6 miscarriages) and 8 control ETP samples. RNA-Seq and miRNA-Seq were performed on Illumina HiSeq2000 platform. Data analysis was implemented using DeSeq2 programme.

Results: Our data shows that in the placentas from RPL cases, the majority of differentially expressed genes are downregulated. These genes are explicitly involved in the basic machinery required for replication and chromatin integrity, transcription and RNA processing, maintenance of mitochondria and other essential genome functions required in the process of rapid cellular proliferation and differentiation critical in early placental development. The identified genes with increased transcript levels confirmed several loci previously linked to placental malfunction in RPL pregnancies. Most importantly, a large fraction of differentially expressed genes in RPL possess binding sites for E2F transcription factors known to be involved in regulating the replication machinery of the mammalian endocycle – a key process to guarantee normal trophoblast proliferation and invasion, placental development, and fetal viability.

Conclusion: The list of differentially expressed genes in RPL represents a source for generating mouse models to investigate in vivo treatment options for RPL, for screening genetic variants predisposing to pregnancy failure and for developing biomarkers for monitoring of early pregnancies in clinical risk cases

Reference: Siim Sõber, Kristiina Rull, Mario Reiman, Piret Ilisson, Pirkko Mattila, Maris Laan “RNA sequencing of chorionic villi from recurrent pregnancy loss patients reveals impaired function of basic nuclear and cellular machinery” (In manuscript).