{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T01:31:25Z","timestamp":1778895085442,"version":"3.51.4"},"reference-count":62,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T00:00:00Z","timestamp":1700784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo State Research Foundation (FAPESP)","doi-asserted-by":"publisher","award":["2014\/04193-0"],"award-info":[{"award-number":["2014\/04193-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019 responses to levothyroxine. The RT-qPCR demonstrated a difference in OR6X1 and OR4E2 expression between GHT and healthy pregnancy (p &lt; 0.05). Those genes presented a negative correlation with TSH (r: \u22120.51, p &lt; 0.05; and r: \u22120.44, p &lt; 0.05), a strong positive correlation with each other (r: 0.89; p &lt; 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.<\/jats:p>","DOI":"10.3390\/ijms242316681","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T03:43:59Z","timestamp":1700797439000},"page":"16681","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exploring the Potential of Olfactory Receptor Circulating RNA Measurement for Preeclampsia Prediction and Its Linkage to Mild Gestational Hypothyroidism"],"prefix":"10.3390","volume":"24","author":[{"given":"Andr\u00e9a Harumy de Lima","family":"Hirata","sequence":"first","affiliation":[{"name":"Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (Uninove), Rua Vergueiro, 235\/249, S\u00e3o Paulo 01525-000, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiz Ant\u00f4nio de Jesus Rocha","family":"Camargo","sequence":"additional","affiliation":[{"name":"Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (Uninove), Rua Vergueiro, 235\/249, S\u00e3o Paulo 01525-000, SP, Brazil"},{"name":"Thyroid Diseases Center, Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, Rua Pedro de Toledo 669, 11th Floor, S\u00e3o Paulo 04039-032, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valdelena Alessandra da","family":"Silva","sequence":"additional","affiliation":[{"name":"Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (Uninove), Rua Vergueiro, 235\/249, S\u00e3o Paulo 01525-000, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robson Jos\u00e9 de","family":"Almeida","sequence":"additional","affiliation":[{"name":"Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (Uninove), Rua Vergueiro, 235\/249, S\u00e3o Paulo 01525-000, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas dos Santos","family":"Bacigalupo","sequence":"additional","affiliation":[{"name":"Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (Uninove), Rua Vergueiro, 235\/249, S\u00e3o Paulo 01525-000, SP, Brazil"},{"name":"Department of Obstetrics and Gynecology, Conjunto Hospitalar do Mandaqui, Rua Volunt\u00e1rios da P\u00e1tria, 4301, S\u00e3o Paulo 02401-400, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Clara","family":"Albejante","sequence":"additional","affiliation":[{"name":"Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (Uninove), Rua Vergueiro, 235\/249, S\u00e3o Paulo 01525-000, SP, Brazil"},{"name":"Department of Obstetrics and Gynecology, Conjunto Hospitalar do Mandaqui, Rua Volunt\u00e1rios da P\u00e1tria, 4301, S\u00e3o Paulo 02401-400, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavia Salom\u00e3o d\u2019Avila","family":"Curi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Conjunto Hospitalar do Mandaqui, Rua Volunt\u00e1rios da P\u00e1tria, 4301, S\u00e3o Paulo 02401-400, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2165-0761","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Varela","sequence":"additional","affiliation":[{"name":"Center for Research and Molecular Diagnostic of Genetic Diseases, Department of Biophysics, Universidade Federal de S\u00e3o Paulo (UNIFESP), Rua Pedro de Toledo 669, 9th Floor, S\u00e3o Paulo 04039-032, SP, Brazil"},{"name":"McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3524-4876","authenticated-orcid":false,"given":"Leonardo","family":"Martins","sequence":"additional","affiliation":[{"name":"Center for Research and Molecular Diagnostic of Genetic Diseases, Department of Biophysics, Universidade Federal de S\u00e3o Paulo (UNIFESP), Rua Pedro de Toledo 669, 9th Floor, S\u00e3o Paulo 04039-032, SP, Brazil"},{"name":"Division of Medical Sciences, Laboratory of Transcriptional Regulation, Institute of Medical Biology of Polish Academy of Sciences (IMB-PAS), Lodowa 106, 93-232 \u0141\u00f3d\u017a, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Bosco","family":"Pesquero","sequence":"additional","affiliation":[{"name":"Center for Research and Molecular Diagnostic of Genetic Diseases, Department of Biophysics, Universidade Federal de S\u00e3o Paulo (UNIFESP), Rua Pedro de Toledo 669, 9th Floor, S\u00e3o Paulo 04039-032, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Humberto","family":"Delle","sequence":"additional","affiliation":[{"name":"Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (Uninove), Rua Vergueiro, 235\/249, S\u00e3o Paulo 01525-000, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8653-0031","authenticated-orcid":false,"given":"Cleber P.","family":"Camacho","sequence":"additional","affiliation":[{"name":"Molecular Innovation and Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (Uninove), Rua Vergueiro, 235\/249, S\u00e3o Paulo 01525-000, SP, Brazil"},{"name":"Thyroid Diseases Center, Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, Rua Pedro de Toledo 669, 11th Floor, S\u00e3o Paulo 04039-032, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mahadik, K., Choudhary, P., and Roy, P.K. (2020). Study of thyroid function in pregnancy, its feto-maternal outcome; a prospective observational study. BMC Pregnancy Childbirth, 20.","DOI":"10.1186\/s12884-020-03448-z"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1089\/thy.2019.0199","article-title":"The Impact of Thyroid Disorders on Clinical Pregnancy Outcomes in a Real-World Study Setting","volume":"30","author":"Sitoris","year":"2020","journal-title":"Thyroid"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S2213-8587(22)00007-9","article-title":"Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: A systematic review and individual-participant data meta-analysis","volume":"10","author":"Toloza","year":"2022","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1089\/thy.2018.0311","article-title":"Pregnancy and Perinatal Outcome Among Hypothyroid Mothers: A Population-Based Cohort Study","volume":"29","author":"Turunen","year":"2019","journal-title":"Thyroid"},{"key":"ref_5","first-page":"387","article-title":"Thyroid dysfunction and pregnancy outcomes","volume":"13","author":"Nazarpour","year":"2015","journal-title":"Iran. J. Reprod. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3312","DOI":"10.1210\/clinem\/dgab503","article-title":"Women with Chronic Hypoparathyroidism Have Low Risk of Adverse Pregnancy Outcomes","volume":"106","author":"Bjornsdottir","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1097\/AOG.0b013e3181788dd7","article-title":"Maternal thyroid hypofunction and pregnancy outcome","volume":"112","author":"Malone","year":"2008","journal-title":"Obstet. Gynecol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1210\/jc.2009-1904","article-title":"Thyroid dysfunction and autoantibodies during pregnancy as predictive factors of pregnancy complications and maternal morbidity in later life","volume":"95","author":"Pouta","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1089\/thy.2015.0418","article-title":"Subclinical Hypothyroidism in Pregnancy: A Systematic Review and Meta-Analysis","volume":"26","author":"Maraka","year":"2016","journal-title":"Thyroid"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"759064","DOI":"10.3389\/fendo.2022.759064","article-title":"Levothyroxine Supplementation in Euthyroid Pregnant Women with Positive Autoantibodies: A Systematic Review and Meta-Analysis","volume":"13","author":"Liberati","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e275","DOI":"10.1055\/s-0039-1695004","article-title":"Lasting Effects of Intrauterine Exposure to Preeclampsia on Offspring and the Underlying Mechanism","volume":"9","author":"Lu","year":"2019","journal-title":"Am. J. Perinatol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1007\/s12020-022-02982-4","article-title":"Thyroid disorders and cardiovascular manifestations: An update","volume":"75","author":"Paschou","year":"2022","journal-title":"Endocrine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1210\/jcem.87.5.8464","article-title":"The role of thyroid hormone in blood pressure homeostasis: Evidence from short-term hypothyroidism in humans","volume":"87","author":"Fommei","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1089\/thy.2014.0028","article-title":"Guidelines for the treatment of hypothyroidism: Prepared by the american thyroid association task force on thyroid hormone replacement","volume":"24","author":"Jonklaas","year":"2014","journal-title":"Thyroid"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1210\/jc.2017-01144","article-title":"Thyroid State Regulates Gene Expression in Human Whole Blood","volume":"103","author":"Massolt","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1056\/NEJMoa1110296","article-title":"A mutation in the thyroid hormone receptor alpha gene","volume":"366","author":"Bochukova","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1161\/01.RES.88.3.313","article-title":"Thyroid hormone activation in human vascular smooth muscle cells: Expression of type II iodothyronine deiodinase","volume":"88","author":"Mizuma","year":"2001","journal-title":"Circ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1677\/jme.0.0230241","article-title":"Differential expression of thyroid hormone receptor isoforms is strikingly related to cardiac and skeletal muscle phenotype during postnatal development","volume":"23","author":"White","year":"1999","journal-title":"J. Mol. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.ando.2018.09.008","article-title":"TRalpha inhibits arterial renin-angiotensin system expression and prevents cholesterol accumulation in vascular smooth muscle cells","volume":"80","author":"Neggazi","year":"2019","journal-title":"Ann. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/100202a0","article-title":"The Thyroid Gland in Health and Disease","volume":"100","author":"Herring","year":"1917","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/0002-9343(75)90394-0","article-title":"Defects of taste and smell in patients with hypothyroidism","volume":"59","author":"McConnell","year":"1975","journal-title":"Am. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Baskoy, K., Ay, S.A., Altundag, A., Kurt, O., Salihoglu, M., Deniz, F., Tekeli, H., Yonem, A., and Hummel, T. (2016). Is There Any Effect on Smell and Taste Functions with Levothyroxine Treatment in Subclinical Hypothyroidism?. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149979"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0165-3806(87)90022-8","article-title":"Loss of sense of smell in adult, hypothyroid mice","volume":"433","author":"Beard","year":"1987","journal-title":"Dev. Brain Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1002\/alr.21565","article-title":"Evaluation of olfactory function in adults with primary hypothyroidism","volume":"5","author":"Gunbey","year":"2015","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_25","first-page":"577","article-title":"Olfaction in congenital hypothyroidism","volume":"56","author":"Walczak","year":"2002","journal-title":"Otolaryngol. Pol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1073\/pnas.0307882100","article-title":"The human olfactory receptor gene family","volume":"101","author":"Malnic","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1073\/pnas.0308051100","article-title":"The mouse olfactory receptor gene family","volume":"101","author":"Godfrey","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/0092-8674(91)90418-X","article-title":"A novel multigene family may encode odorant receptors: A molecular basis for odor recognition","volume":"65","author":"Buck","year":"1991","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6439","DOI":"10.1038\/s41598-020-63040-5","article-title":"Circulating RNA Transcriptome of Pregnant Women with TSH Just Above the Trimester-Specific Reference and its Correlation with the Hypertensive Phenotype","volume":"10","author":"Bacigalupo","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Flegel, C., Manteniotis, S., Osthold, S., Hatt, H., and Gisselmann, G. (2013). Expression profile of ectopic olfactory receptors determined by deep sequencing. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055368"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eadf3026","DOI":"10.1126\/sciadv.adf3026","article-title":"Hypoxia sensing requires H(2)S-dependent persulfidation of olfactory receptor 78","volume":"9","author":"Peng","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"945","DOI":"10.3109\/09513590.2015.1065483","article-title":"Comparison of maternal and umbilical cord blood HIF-1\u03b1 and nitric oxide levels in early and late onset preeclamptic pregnancies","volume":"31","author":"Zafer","year":"2015","journal-title":"Gynecol. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1152\/jn.00067.2021","article-title":"Role of olfactory receptor78 in carotid body-dependent sympathetic activation and hypertension in murine models of chronic intermittent hypoxia","volume":"125","author":"Peng","year":"2021","journal-title":"J. Neurophysiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e15017","DOI":"10.14814\/phy2.15017","article-title":"Olfactory receptor 78 modulates renin but not baseline blood pressure","volume":"9","author":"Poll","year":"2021","journal-title":"Physiol. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4410","DOI":"10.1073\/pnas.1215927110","article-title":"Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation","volume":"110","author":"Pluznick","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13041-022-00917-8","article-title":"Olfactory receptor 78 is expressed in hypothalamic vasopressin\/oxytocin neurons, parenchymal microglia and choroidal macrophages in mice","volume":"15","author":"Nakashima","year":"2022","journal-title":"Mol. Brain"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s00467-015-3181-8","article-title":"How does your kidney smell? Emerging roles for olfactory receptors in renal function","volume":"31","author":"Shepard","year":"2016","journal-title":"Pediatr. Nephrol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1073\/pnas.0812859106","article-title":"Functional expression of the olfactory signaling system in the kidney","volume":"106","author":"Pluznick","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","first-page":"975","article-title":"Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats","volume":"118","author":"Simonides","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1080\/09513590.2016.1240774","article-title":"D2-Thr92Ala, thyroid hormone levels and biochemical hypothyroidism in preeclampsia","volume":"33","author":"Procopciuc","year":"2017","journal-title":"Gynecol. Endocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"612","DOI":"10.5483\/BMBRep.2012.45.11.232","article-title":"Olfactory receptors in non-chemosensory tissues","volume":"45","author":"Kang","year":"2012","journal-title":"BMB Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1152\/physrev.00013.2017","article-title":"Human Olfactory Receptors: Novel Cellular Functions Outside of the Nose","volume":"98","author":"Massberg","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"R27","DOI":"10.1530\/JOE-16-0340","article-title":"Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia","volume":"232","author":"Boeldt","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.12669\/pjms.345.15719","article-title":"Expression and Clinical Significance of Serum 25-OH-D in pregnant women with SCH (Subclinical Hypothyroidism) and GDM (Gestational Diabetes Mellitus)","volume":"34","author":"Zhou","year":"2018","journal-title":"Pak. J. Med. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13058-018-0933-y","article-title":"HER2 is not a cancer subtype but rather a pan-cancer event and is highly enriched in AR-driven breast tumors","volume":"20","author":"Daemen","year":"2018","journal-title":"Breast Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.placenta.2015.05.017","article-title":"ERBB2 gene amplification increases during the transition of proximal EGFR(+) to distal HLA-G(+) first trimester cell column trophoblasts","volume":"36","author":"Meinhardt","year":"2015","journal-title":"Placenta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"765406","DOI":"10.1155\/2015\/765406","article-title":"Are Thyroid Hormone and Tumor Cell Proliferation in Human Breast Cancers Positive for HER2 Associated?","volume":"2015","author":"Mourouzis","year":"2015","journal-title":"Int. J. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5213","DOI":"10.1210\/jc.2004-0352","article-title":"Effects of 3,5,3\u2032-triiodothyronine on the invasive potential and the expression of integrins and matrix metalloproteinases in cultured early placental extravillous trophoblasts","volume":"89","author":"Oki","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1093\/biolre\/ioy047","article-title":"Mechanisms for the establishment and maintenance of pregnancy: Synergies from scientific collaborations","volume":"99","author":"Bazer","year":"2018","journal-title":"Biol. Reprod."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.bbrc.2015.03.046","article-title":"Expression of human olfactory receptor 10J5 in heart aorta, coronary artery, and endothelial cells and its functional role in angiogenesis","volume":"460","author":"Kim","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Liou, L., Hornburg, M., and Robertson, D.S. (2023). Global FDR control across multiple RNAseq experiments. Bioinformatics, 39.","DOI":"10.1093\/bioinformatics\/btac718"},{"key":"ref_52","unstructured":"American College of Obstetricians and Gynecologists (2013). Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists\u2019 Task Force on Hypertension in Pregnancy. Obstet. Gynecol., 122, 1122\u20131131."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"100323","DOI":"10.1016\/j.xcrm.2021.100323","article-title":"Crowdsourcing assessment of maternal blood multi-omics for predicting gestational age and preterm birth","volume":"2","author":"Tarca","year":"2021","journal-title":"Cell Rep. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1089\/thy.2016.0457","article-title":"2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum","volume":"27","author":"Alexander","year":"2017","journal-title":"Thyroid"},{"key":"ref_55","unstructured":"R Core Team (2019). R: A Language and Environment for Statistical Computing, 3.4.1 (2017-06-30) ed., R Foundation for Statistical Computing. Available online: https:\/\/www.R-project.org\/."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Marini, F., and Binder, H. (2019). pcaExplorer: An R\/Bioconductor package for interacting with RNA-seq principal components. BMC Bioinform., 20.","DOI":"10.1186\/s12859-019-2879-1"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Heberle, H., Meirelles, G.V., da Silva, F.R., Telles, G.P., and Minghim, R. (2015). InteractiVenn: A web-based tool for the analysis of sets through Venn diagrams. BMC Bioinform., 16.","DOI":"10.1186\/s12859-015-0611-3"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3718","DOI":"10.1093\/bioinformatics\/btv428","article-title":"Dendextend: An R package for visualizing, adjusting and comparing trees of hierarchical clustering","volume":"31","author":"Galili","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.3758\/BRM.41.4.1149","article-title":"Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses","volume":"41","author":"Faul","year":"2009","journal-title":"Behav. Res. Methods"},{"key":"ref_61","unstructured":"Galen, R.S., and Gambino, S.R. (1975). Beyond Normality: The Predictive Value and Efficiency of Medical Diagnoses, Wiley."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/1097-0142(1950)3:1<32::AID-CNCR2820030106>3.0.CO;2-3","article-title":"Index for rating diagnostic tests","volume":"3","author":"Youden","year":"1950","journal-title":"Cancer"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/23\/16681\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:28:52Z","timestamp":1760131732000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/23\/16681"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,24]]},"references-count":62,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["ijms242316681"],"URL":"https:\/\/doi.org\/10.3390\/ijms242316681","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,24]]}}}