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

• Published in: International journal of molecular sciences Vol. 24; no. 23; p. 16681
• Main Authors: Hirata, Andréa Harumy de Lima, Camargo, Luiz Antônio de Jesus Rocha, Silva, Valdelena Alessandra da, Almeida, Robson José de, Bacigalupo, Lucas Dos Santos, Albejante, Maria Clara, Curi, Flavia Salomão d'Avila, Varela, Patrícia, Martins, Leonardo, Pesquero, João Bosco, Delle, Humberto, Camacho, Cleber P
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2023
• Subjects: Analysis; Biomarkers; Blood pressure; Cell-Free Nucleic Acids; circulating RNA; Cluster analysis; Female; Gene expression; Genes; Gestational age; Humans; Hypertension; Hypothyroidism; Hypothyroidism - genetics; Hypoxia; Measurement; mild gestational hypothyroidism; olfactory receptor; Pre-Eclampsia - genetics; predictive biomarkers; Preeclampsia; Pregnancy; Proteins; Receptors, Odorant - genetics; RNA; Thyroid gland; Thyroxine; transcriptome; Massachusetts; predictive biomarkers; circulating RNA; mild gestational hypothyroidism; preeclampsia; olfactory receptor; transcriptome
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms242316681

Gestational hypothyroidism may lead to preeclampsia development. However, this pathophysiological is unknown. We expect to find a shared mechanism by comparing hypothyroidism and preeclampsia. From our transcriptome data, we recognized olfactory receptors as that fingerprint. The reduction of taste and smell in hypothyroid patients has been known for a long time. Therefore, we decided to look to the olfactory receptors and aimed to identify genes capable of predicting preeclampsia (PEC). Methods: An Ion Proton Sequencer (Thermo Fisher Scientific, Waltham, MA, USA) was used to construct the transcriptome databases. RStudio with packages Limma v.3.50.0, GEOquery v.2.62.2, and umap v.0.2.8.8 were used to analyze the differentially expressed genes in GSE149440 from the Gene Expression Omnibus (GEO). The 7500 Real-Time PCR System (Applied Biosystems, Foster City, CA, USA) was used for RT-qPCR amplification of and . Results: Our transcriptomic datasets analysis revealed 25.08% and 26.75% downregulated olfactory receptor (ORs) in mild nontreated gestational hypothyroidism (GHT) and PEC, respectively. In the GSE149440 GEO dataset, we found , , , , , , and as predictors of early-onset PEC. We also evaluate two chosen biomarkers' responses to levothyroxine. The RT-qPCR demonstrated a difference in and expression between GHT and healthy pregnancy ( < 0.05). Those genes presented a negative correlation with TSH (r: -0.51, < 0.05; and r: -0.44, < 0.05), a strong positive correlation with each other (r: 0.89; < 0.01) and the levothyroxine-treated group had no difference from the healthy one. We conclude that ORs could be used as biomarkers at the beginning of gestation, and the downregulated ORs found in GHT may be improved with levothyroxine treatment.