Circulating RNA Transcriptome of Pregnant Women with TSH Just Above the Trimester-Specific Reference and its Correlation with the Hypertensive Phenotype

Abstract

During gestation, a woman's body undergoes physiological changes that alter thyroid function. pregnant women with hypothyroidism may exhibit gestational complications, including hypertension and preeclampsia. We investigated differentially expressed genes (DEGs) in circulating RNAs from pregnant women with tSH levels just above the normal range to determine the impact of a mild elevation of TSH in pregnancy. We selected three women with healthy thyroid pregnancy (HTP), three pregnant women with gestational hypothyroidism (GHT), and three nonpregnant women (NPG) to construct transcriptome libraries. We also compared our results with data from the GEO dataset and DisGeNET. We identified 1500 DEG in GHT and 1656 DEG in HTP. From GEO dataset, we recognized 453 DEGs in trimester-specific plasma RNA, 1263 DEGs in placental tissues from healthy women, 1031 DEGs from preeclamptic uteroplacental tissues and 1657 DEGs from placental tissues from severely preeclamptic women. In this scenario, 12.26% and 12.86% genes were shared between these datasets in GHT and HTP, respectively. We stablished 62 genes in GHT DEGs related to hypertensive phenotype hallmarks. In conclusion, even in women with a mild TSH increment, we were able to detect some DEGs that could be associated with a hypertensive phenotype.Circulating Ribonucleic Acid (RNA) represents a powerful strategy, less invasive and capable of real-time tracking diseases. The circulating protein codifying transcripts (mRNA, messenger RNA) may also provide clinically useful additional information when compared to the direct protein measurement 1 . This strategy is also sensible enough to detect fetal RNA circulating in the mother's blood 2 . The use of corticotropin-releasing hormone (CRH) mRNA detection in pregnancy was also reported to be capable of working as a molecular marker for preeclampsia 3 . Nevertheless, the transcriptome analysis is efficient enough to offer much more information than the use of a single RNA. The target RNA detection strategies, like RNA-Seq, can be performed in a simple blood sample and can give us the quantitative expression of the coding and noncoding RNA from the mother, the placenta or the fetus in a unique and noninvasive way 4 .During gestation, a woman's body undergoes physiological changes that alter thyroid function and thyroid hormone metabolism. Most of these changes are related to the increased demand for thyroid hormone by the mother and the fetus, the placental degradation of the hormone and the increase in the thyroxin-binding globulin (TBG) concentration. TBG increases due to an estrogenic stimulus during pregnancy, and for this reason, free thyroxine (FT 4 ) is highly influenced by the significant increase in the thyroxine (T 4 )-bound fraction.

Maternal, neonatal, pregnancy outcome characteristics of pregnant women with high plasma cell-free DNA concentration in non-invasive prenatal screening: a retrospective analysis

“…It is uncertain whether GHT is associated with increased cfDNA concentrations. Notably, Hirata et al studied differentially expressed genes in the circulating RNA of pregnant women with TSH levels marginally higher than the normal range and found that high levels of circulating RNA could be detected, even in women with mildly elevated TSH ( 12 ). SLE is an autoimmune disease that causes damage in parts of the body, including skin, kidneys, and joints and is characterised by the production of antibodies against nuclear antigens known as “anti-nuclear antibodies.” Recent research has shown that compared with healthy controls, SLE patients have higher cfDNA levels.…”

Exploring the Potential of Olfactory Receptor Circulating RNA Measurement for Preeclampsia Prediction and Its Linkage to Mild Gestational Hypothyroidism

“…Our previous study found 1656 DEGs in healthy-thyroid pregnancy (HTP) using a healthy nonpregnant woman set, showing the physiologic mechanism regulated by genes in a healthy pregnancy [29]. Three hundred and four ORs found in HTP were similar between GHT and PEC, and all were upregulated in a healthy pregnancy condition (Supplementary Table S1).…”