PhD Scientific Days 2023

Translational Medicine - Posters O

Identification of Disrupted Molecular Pathways and Promising Biomarkers for Recurrent Pregnancy Loss Using Systems Biology

Text of the abstract

Miscarriages are a significant problem with nearly 20% of clinically recognized pregnancies and 50-70% of conceptions ending in pregnancy loss. Recurrent pregnancy loss (RPL) affects 1-5% of clinically recognized pregnancies and involves the loss of two or more consecutive pregnancies before 20 weeks of gestation. The causes and molecular pathways of RPL remain poorly understood, posing challenges in developing reliable screening tools or effective preventive treatments.
To discover the molecular pathways of RPL, we employed a hypothesis-free systems biology approach. Placental samples from 8 patients with RPL and 8 gestational age-matched controls at 8-12 weeks of gestation were analyzed using histopathology, whole-genome microarray, and several bioinformatic tools. Additionally, we conducted next-generation proteomics studies on blood samples from the same group of women (n=16), obtained during surgery.
We identified 1,537 genes that were differentially expressed in RPL. Notably, there was an over-representation of placenta-specific genes (n=113, OR: 31.8, p=4.410-88) and villous trophoblast differentiation-related genes (n=398, OR: 3.8, p=5.610-80). Of these genes, 98% and 83% were downregulated, respectively, indicating a significant impairment of trophoblastic functions in RPL. Furthermore, immune-associated genes were enriched, with upregulation of proinflammatory genes and downregulation of anti-inflammatory genes. We observed activation of graft rejection and autoimmune pathways. We also identified disturbed gene modules and their potential drug-target hub-genes in RPL. To validate the transcriptomic findings, we used qPCR to confirm the differential expression of 10 genes. Additionally, we found decreased levels of placental protein products in the maternal blood proteome, which may serve as potential biomarker candidates for RPL, given their relation to placental gene expression changes.
The outcomes of our study may advance the comprehension of the molecular mechanisms underlying RPL, and may aid in identifying drug molecules as potential therapeutic targets. However, the potential biomarkers we identified must be verified in more comprehensive clinical investigations.
This research was supported by the Hungarian Academy of Sciences Momentum “LP2014-7/2014 and the Hungarian National Research, Development and Innovation Fund grant “FIEK_16-1-2016-0005.