Systemic lupus erythematosus dysregulates the expression of long noncoding RNAs in placentas.

BACKGROUND: Systemic lupus erythematosus (SLE) can cause placental dysfunctions, which may result in pregnancy complications. Long noncoding RNAs (lncRNAs) are actively involved in the regulation of immune responses during pregnancy. The present study aimed to determine the lncRNA expression profiles in placentas from women with SLE to gain new insights into the underlying molecular mechanisms in SLE pregnancies. METHODS: RNA sequencing (RNA-seq) analysis was performed to identify SLE-dysregulated lncRNAs and mRNAs in placentas from women with SLE and normal full-term (NT) pregnancies. Bioinformatics analysis was conducted to predict the biological functions of these SLE-dysregulated lncRNAs and mRNAs. RESULTS: RNA-seq analysis identified 52 dysregulated lncRNAs in SLE placentas, including 37 that were upregulated and 15 downregulated. Additional 130 SLE-dysregulated mRNAs were discovered, including 122 upregulated and 8 downregulated. Bioinformatics analysis revealed that SLE-dysregulated genes were associated with biological functions and gene networks, such as regulation of type I interferon-mediated signaling pathway, response to hypoxia, regulation of MAPK (mitogen-activated protein kinase) cascade, response to steroid hormone, complement and coagulation cascades, and Th1 and Th2 cell differentiation. CONCLUSIONS: This is the first report of the lncRNA profiles in placentas from SLE pregnancies. These results suggest that the aberrant expression and the potential regulatory function of lncRNAs in placentas may play comprehensive roles in the pathogenesis of SLE pregnancies. SLE-dysregulated lncRNAs may potentially serve as biomarkers for SLE.

Sexual Dimorphisms of Protein-Coding Gene Profiles in Placentas From Women With Systemic Lupus Erythematosus.

Background: Systemic lupus erythematosus (SLE) may cause pathogenic changes in the placentas during human pregnancy, such as decreased placental weight, intraplacental hematoma, ischemic hypoxic change, placental infarction, and decidual vasculopathy, which contribute to high maternal and fetal mortality and morbidity. Sex-specific adaptations of the fetus are associated with SLE pregnancies. The present study aimed to determine the transcriptomic profiles of female and male placentas from women with SLE. Methods: RNA sequencing (RNA-seq) was performed to identify differentially expressed protein-coding genes (DEGs) in placentas from women with SLE vs. normal term (NT) pregnancies with female and male fetuses (n = 3-5/sex/group). Real-time-quantitative PCR was performed (n = 4 /sex/group) to validate the RNA-seq results. Bioinformatics functional analysis was performed to predict the biological functions and pathways of SLE-dysregulated protein-coding genes. Results: Compared with NT-female (NT-F) placentas, 119 DEGs were identified in SLE-female (SLE-F) placentas. Among these 119 DEGs, five and zero are located on X- and Y-chromosomes, respectively, and four are located on the mitochondrial genome. Compared with NT-male (NT-M) placentas, 458 DEGs were identified in SLE-male (SLE-M) placentas, among which 16 are located on the X-chromosome and zero on the Y-chromosome and mitochondrial genome. Twenty-four DEGs were commonly dysregulated in SLE-F and -M placentas. Functional analysis showed that SLE-dysregulated protein-coding genes were associated with diverse biological functions and pathways, including angiogenesis, cellular response to growth factor stimulus, heparin-binding, HIF (hypoxia-inducible factor)-1 signaling pathway, and Interleukin-17 (IL-17) signaling pathway in both SLE-F and -M placentas. Biological regulations were differentially enriched between SLE-F and -M placentas. Regulation of blood circulation, response to glucocorticoid, and rhythmic process were all enriched in SLE-F, but not SLE-M placentas. In contrast, tumor necrosis factor production, Th17 cell differentiation, and MDA (melanoma differentiation-associated gene)-5 signaling pathway were enriched in SLE-M but not SLE-F placentas. Conclusion: This report investigated the protein-coding gene profiles of placenta tissues from SLE patients using RNA-seq. The results suggest that the SLE-dysregulated protein-coding genes in placentas may contribute to the pathophysiological progress of SLE pregnancies in a fetal sex-specific manner, leading to adverse pregnancy outcomes.