Selenium-Related Gene Activation in Fetal Growth Restriction Placentas: A Bioinformatics Analysis

AUTOR(I) / AUTHOR(S): Aleksandar Rakić, Jelena Brakus, Nikoleta Lugonja, Jelena Milić

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DOI:  10.46793/ICCBIKG25.445R

SAŽETAK / ABSTRACT:

Selenium is a crucial trace element of significant importance for human health, encompassing muscle function, male reproductive biology, cardiovascular health, endocrine regulation, nervous system function, and particularly immune system efficacy. It is a fundamental structural element of numerous enzymes, including glutathione peroxidase, thioredoxin reductase, and deiodinases. These enzymes are crucial for antioxidation, reproduction, muscular function, and tumor prevention. Finally, regarding pregnancy, studies have shown that both excess and shortage of selenium are linked to spontaneous abortion, pre- eclampsia, gestational diabetes, fetal growth restriction, and preterm birth. We used publicly available RNA-seq datasets from the Gene Expression Omnibus (GEO): GSE203507 and GSE114691. We analyzed differentially expressed genes between fetal growth restriction (FGR) and term birth (TB) placental villous in GEO2R. In GSE203507 dataset we selected villous tissue samples (FGR: n = 5, TB: n = 5), along with the genes of interest and further analyzed gene expression using Mann–Whitney U tests and violin plots. Functional pathway enrichment was evaluated using Gene Set Enrichment Analysis (GSEA) with Reactome gene sets. We used the independent GSE114691 dataset for validation of key genes expression and pathway signals. The results of our study revealed the significantly higher expression of essential antioxidant selenoproteins in placental tissue affected by FGR, specifically Glutathione Peroxidase 1 (GPX1) and Methionine Sulfoxide Reductase B1 (MSRB1). Mann–Whitney U test validated the mentioned increase with p-values of 0.0317 and 0.0079, respectively. Furthermore, we conducted a Gene Set Enrichment Analysis (GSEA). The pathway related to “Selenoamino Acid Metabolism” (REACTOME) showed significant enrichment in FGR tissue samples compared term birth placentas (NES = 1.84, FDR q = 0.019). These results could indicate the activation of the molecular mechanisms involved in biosynthesis and incorporation of selenocysteine. The GSE114691 dataset confirmed these results, revealing significantly altered expression of both GPX1 and MSRB1 in placental villous tissues impacted by FGR. MSRB1 exhibited significant upregulation (log₂FC = +0.41, FDR = 0.00294). Additionally, GSEA conducted on the validation set confirmed the enrichment of the selenoamino acid metabolism pathway, confirming the resilience and reproducibility of the transcriptome signature across diverse cohorts. The results of our study indicated the potential significance of selenium and selenoproteins, as well as the molecular pathways in which they are involved, in the development of fetal growth restriction. Given the known role of oxidative stress in the development of disorders such as FGR, as well as the antioxidant properties of selenium itself and the signaling pathways it configures, this study could have an impact on future research on diagnostic knowledge, as well as selenium supplementation in these high-risk pregnancies.

KLJUČNE REČI / KEYWORDS:

fetal growth restriction; selenium; selenoproteins; bioinformatics; transcriptomics

PROJEKAT / ACKNOWLEDGEMENT:

This research has been financially supported by the Ministry of Science, Technological Development and Innovation of the Republic of Serbia (Contract No. 451-03-136/2025- 03/200026). This work is related to the implementation of the United Nations Sustainable Development Goal 3 – Good health and well-being.

LITERATURA / REFERENCES:

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