Placental transcriptome analysis of hypertensive pregnancies identifies distinct gene expression profiles of preeclampsia superimposed on chronic hypertension

BMC Medical Genomics

Research

Olesya Plazyo¹  Johann E. Gudjonsson¹  Santhi K. Ganesh²  Elizabeth S. Langen³  Ashley M. Hesson³ 

[1] Departments of Dermatology and Immunology, University of Michigan, 48109, Ann Arbor, MI, USA;Division of Cardiovascular Medicine, Department of Internal Medicine, Department of Human Genetics, University of Michigan, MSRB III / Room 7220A, 1150 West Medical Center Dr., 48109, Ann Arbor, MI, USA;Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Michigan, 1500 East Medical Center Dr., 48109, Ann Arbor, MI, USA;

关键词: Biomarkers;    Inhibin;    Preeclampsia;    RNASeq;    Hypertension;   

DOI  :  10.1186/s12920-023-01522-x

 received in 2022-04-17, accepted in 2023-04-20,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe pathogenesis of preeclampsia superimposed on chronic hypertension (SI) is poorly understood relative to preeclampsia (PreE) occurring in pregnant people without chronic hypertension. Placental transcriptomes in pregnancies complicated by PreE and SI have not been previously compared.MethodsWe identified pregnant people in the University of Michigan Biorepository for Understanding Maternal and Pediatric Health with hypertensive disorders affecting singleton, euploid gestations (N = 36) along with non-hypertensive control subjects (N = 12). Subjects were grouped as: (1) normotensive (N = 12), (2) chronic hypertensive (N = 13), (3) preterm PreE with severe features (N = 5), (4) term PreE with severe features (N = 11), (5) preterm SI (N = 3), or (6) term SI (N = 4). Bulk RNA sequencing of paraffin-embedded placental tissue was performed. The primary analysis assessed differential gene expression relative to normotensive and chronic hypertensive placentas, where Wald adjusted P values < 0.05 were considered significant. Unsupervised clustering analyses and correlation analyses were performed between conditions of interest, and a gene ontology was constructed.ResultsComparing samples from pregnant people with hypertensive diseases to non-hypertensive controls, there were 2290 differentially expressed genes. The log2-fold changes in genes differentially expressed in chronic hypertension correlated better with term (R = 0.59) and preterm (R = 0.63) PreE with severe features than with term (R = 0.21) and preterm (R = 0.22) SI. A relatively poor correlation was observed between preterm SI and preterm PreE with severe features (0.20) as well as term SI and term PreE with severe features (0.31). The majority of significant genes were downregulated in term and preterm SI versus normotensive controls (92.1%, N = 128). Conversely, most term and preterm PreE with severe features genes were upregulated compared to the normotensive group (91.8%, N = 97). Many of the upregulated genes in PreE with the lowest adjusted P values are known markers of abnormal placentation (e.g., PAAPA, KISS1, CLIC3), while the downregulated genes with the greatest adjusted P values in SI have fewer known pregnancy-specific functions.ConclusionsWe identified unique placental transcriptional profiles in clinically relevant subgroups of individuals with hypertension in pregnancy. Preeclampsia superimposed on chronic hypertension was molecularly distinct from preeclampsia in individuals without chronic hypertension, and chronic hypertension without preeclampsia, suggesting that preeclampsia superimposed on hypertension may represent a distinct entity.

【 授权许可】

CC BY   
© The Author(s) 2023

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