Molecular pathogenesis of spontaneous abortions – Whole genome copy number analysis and expression of angiogenic factors

Abstract

Objective: To study two major molecular alterations in spontaneous abortions (SA) with unexplained etiology – fetal genomic anomalies and the endometrial expression of main angiogenic factors VEGFA/VEGFR2 and chemokines SDF-1/CXCR4. Materials and methods: Whole genome copy number analysis by arrayCGH or Next Generation Sequencing (NGS) was applied for detection of fetal genomic imbalances. The abortive decidua of SA without fetal aneuploidies was further investigated for expression levels of the abovementioned factors using real time PCR analysis. A total of 30 abortive materials were collected from spontaneous abortions after exclusion of known predisposing factors. Results: In 21 of 30 spontaneous abortions (70%), genomic anomalies were discovered by whole genome copy number analysis. Numerical anomalies were detected in 90% of aberrant cases, and in 10% - structural aberrations were revealed. An increased expression for essential factors of angiogenesis was identified in spontaneous abortions’ tissues - 3.44 times for VEGFA and 10.29 times for VEGFR2. We found an average of 14 times increase in the expression levels of SDF-1 and 3.21 times for its receptor CXCR4. Conclusion: We could suggest the occurrence of increased angiogenesis in SA without fetal aneuploidies, compared to the control tissues, which could lead to increased oxidative stress and fetal loss. Keywords: Spontaneous abortions, Whole genome copy number analysis, ArrayCGH, NGS, Angiogenesis