Dysregulation of Placental Functions and Immune Pathways in Complete Hydatidiform Moles

• Published in: International journal of molecular sciences 2019-10, Vol.20 (20), p.4999
• Main Authors: King, Jennifer R, Wilson, Melissa L, Hetey, Szabolcs, Kiraly, Peter, Matsuo, Koji, Castaneda, Antonio V, Toth, Eszter, Krenacs, Tibor, Hupuczi, Petronella, Mhawech-Fauceglia, Paulette, Balogh, Andrea, Szilagyi, Andras, Matko, Janos, Papp, Zoltan, Roman, Lynda D, Cortessis, Victoria K, Than, Nandor Gabor
• Format: Article
• Language: English
• Subjects: Age; Bioinformatics; Cell adhesion & migration; Choriocarcinoma; Cytokines; Deoxyribonucleic acid; Dimensional analysis; DNA; DNA Methylation; DNA microarrays; Down-Regulation; Epigenetics; Ethnicity; Female; galectin; Gene Expression; Genes; Genomes; Gestational Trophoblastic Disease; Glycoproteins; Growth factors; Hemoglobin; Histones; Hormones; Humans; hydatidiform mole; Hydatidiform Mole - genetics; Hydatidiform Mole - immunology; Immunohistochemistry; Mutation; Paraffins; Pathogenesis; Placenta; Placenta - metabolism; placental-specific gene; Pregnancy - immunology; Pregnancy Trimester, First; Proteins; Systems Biology; trophoblast differentiation; Up-Regulation; Womens health
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20204999

Gene expression studies of molar pregnancy have been limited to a small number of candidate loci. We analyzed high-dimensional RNA and protein data to characterize molecular features of complete hydatidiform moles (CHMs) and corresponding pathologic pathways. CHMs and first trimester placentas were collected, histopathologically examined, then flash-frozen or paraffin-embedded. Frozen CHMs and control placentas were subjected to RNA-Seq, with resulting data and published placental RNA-Seq data subjected to bioinformatics analyses. Paraffin-embedded tissues from CHMs and control placentas were used for tissue microarray (TMA) construction, immunohistochemistry, and immunoscoring for galectin-14. Of the 14,022 protein-coding genes expressed in all samples, 3,729 were differentially expressed (DE) in CHMs, of which 72% were up-regulated. DE genes were enriched in placenta-specific genes (OR = 1.88, = 0.0001), of which 79% were down-regulated, imprinted genes (OR = 2.38, = 1.54 × 10 ), and immune genes (OR = 1.82, = 7.34 × 10 ), of which 73% were up-regulated. DNA methylation-related enzymes and histone demethylases were dysregulated. "Cytokine-cytokine receptor interaction" was the most impacted of 38 dysregulated pathways, among which 17 were immune-related pathways. TMA-based immunoscoring validated the lower expression of galectin-14 in CHM. In conclusion, placental functions were down-regulated, imprinted gene expression was altered, and immune pathways were activated, indicating complex dysregulation of placental developmental and immune processes in CHMs.