| Autor: |
Hirata AHL; Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (Uninove), Rua Vergueiro, 235/249, São Paulo 01525-000, SP, Brazil., Camargo LAJR; Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (Uninove), Rua Vergueiro, 235/249, São Paulo 01525-000, SP, Brazil.; Thyroid Diseases Center, Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, 11th Floor, São Paulo 04039-032, SP, Brazil., Silva VAD; Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (Uninove), Rua Vergueiro, 235/249, São Paulo 01525-000, SP, Brazil., Almeida RJ; Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (Uninove), Rua Vergueiro, 235/249, São Paulo 01525-000, SP, Brazil., Bacigalupo LDS; Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (Uninove), Rua Vergueiro, 235/249, São Paulo 01525-000, SP, Brazil.; Department of Obstetrics and Gynecology, Conjunto Hospitalar do Mandaqui, Rua Voluntários da Pátria, 4301, São Paulo 02401-400, SP, Brazil., Albejante MC; Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (Uninove), Rua Vergueiro, 235/249, São Paulo 01525-000, SP, Brazil.; Department of Obstetrics and Gynecology, Conjunto Hospitalar do Mandaqui, Rua Voluntários da Pátria, 4301, São Paulo 02401-400, SP, Brazil., Curi FSD; Department of Obstetrics and Gynecology, Conjunto Hospitalar do Mandaqui, Rua Voluntários da Pátria, 4301, São Paulo 02401-400, SP, Brazil., Varela P; Center for Research and Molecular Diagnostic of Genetic Diseases, Department of Biophysics, Universidade Federal de São Paulo (UNIFESP), Rua Pedro de Toledo 669, 9th Floor, São Paulo 04039-032, SP, Brazil.; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Martins L; Center for Research and Molecular Diagnostic of Genetic Diseases, Department of Biophysics, Universidade Federal de São Paulo (UNIFESP), Rua Pedro de Toledo 669, 9th Floor, São Paulo 04039-032, SP, Brazil.; Division of Medical Sciences, Laboratory of Transcriptional Regulation, Institute of Medical Biology of Polish Academy of Sciences (IMB-PAS), Lodowa 106, 93-232 Łódź, Poland., Pesquero JB; Center for Research and Molecular Diagnostic of Genetic Diseases, Department of Biophysics, Universidade Federal de São Paulo (UNIFESP), Rua Pedro de Toledo 669, 9th Floor, São Paulo 04039-032, SP, Brazil., Delle H; Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (Uninove), Rua Vergueiro, 235/249, São Paulo 01525-000, SP, Brazil., Camacho CP; Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (Uninove), Rua Vergueiro, 235/249, São Paulo 01525-000, SP, Brazil.; Thyroid Diseases Center, Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, 11th Floor, São Paulo 04039-032, SP, Brazil. |
| Abstrakt: |
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 OR6X1 and OR4E2 . 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 OR5H1 , OR5T3 , OR51A7 , OR51B6 , OR10J5 , OR6C6 , and OR2AG2 as predictors of early-onset PEC. We also evaluate two chosen biomarkers' responses to levothyroxine. The RT-qPCR demonstrated a difference in OR6X1 and OR4E2 expression between GHT and healthy pregnancy ( p < 0.05). Those genes presented a negative correlation with TSH (r: -0.51, p < 0.05; and r: -0.44, p < 0.05), a strong positive correlation with each other (r: 0.89; p < 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. |
