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

Frontiers in Medicine

article

Hui-hui Li¹  Lin-tao Sai³  Shan Tian⁴  Yuan Liu¹  Colman I. Freel²  Kai Wang⁵  Chi Zhou⁶  Jing Zheng²  Qiang Shu⁷  Ying-jie Zhao⁷ 

[1] Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University;Department of Obstetrics and Gynecology, University of Wisconsin-Madison;Department of Infectious Diseases, Qilu Hospital, Cheeloo College of Medicine, Shandong University;Center for Reproductive Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University;Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine;School of Animal and Comparative Biomedical Sciences, University of Arizona;Department of Rheumatology, Qilu Hospital, Cheeloo College of Medicine, Shandong University;Shandong Provincial Clinical Research Center for Immune Diseases and Gout

关键词: systemic lupus erythematosus;    protein-coding RNA;    placenta;    pregnancy;    fetal sex;   

DOI  :  10.3389/fmed.2022.798907

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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