{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:05:57Z","timestamp":1789585557029,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gestational diabetes mellitus (GDM) develops silently during early pregnancy, yet its earliest circulating molecular signatures remain poorly defined. In this exploratory biomarker study, we characterized first-trimester circulating microRNA (miRNAs) associated with later GDM using a pool-based small RNA sequencing approach. Using a systematic and unbiased sequencing strategy with locus-level miRNA resolution, we profiled the first-trimester plasma miRNome and prioritized a set of 18 mature miRNAs from among 255 detected species. Set-level functional enrichment analyses based on curated and predicted miRNA\u2013target interactions derived primarily from cellular and tissue-based studies showed annotation-based convergence on pathways related to Ca2+ homeostasis, glucagon\u2013insulin regulatory circuits, and PI3K\u2013AKT signaling. Network analysis indicated coordinated associations among these miRNAs and shared target pathways involved in insulin secretion and insulin sensitivity. Key contributors\u2014including miR-29a-3p, miR-29c-3p, miR-146a-5p, let-7a-5p, and miR-182-5p\u2014were linked, through in silico target annotation, to central metabolic regulators such as PTEN, PIK3R1, AKT1, AKT2, and components of Ca2+ signaling (ATP2A2, CALM1\/3, ITPR1, RYR2). These circulating miRNAs should be interpreted primarily as biomarkers reflecting coordinated metabolic states rather than as direct causal mediators. Most identified miRNAs have not been previously reported in the context of first-trimester GDM, supporting the exploratory and hypothesis-generating nature of this circulating miRNA signature in early gestational metabolic research.<\/jats:p>","DOI":"10.3390\/ijms27041920","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T13:15:35Z","timestamp":1771334135000},"page":"1920","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An Exploratory Biomarker Study of First-Trimester Circulating miRNAs Associated with Later Gestational Diabetes Mellitus"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8012-3702","authenticated-orcid":false,"given":"Miguel Angel","family":"D\u00e9ctor","sequence":"first","affiliation":[{"name":"Facultad de Agronom\u00eda, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Ex Hacienda El Ca\u00f1ada, General Escobedo 66050, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria Carmen","family":"Mac\u00edas-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Independent Researcher, Garc\u00eda 66024, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"S\u00e1nchez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Facultad de Medicina y Hospital Universitario \u201cDr. Jos\u00e9 Eleuterio Gonz\u00e1lez\u201d, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Mitras Centro, Monterrey 64460, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7809-6888","authenticated-orcid":false,"given":"Armando","family":"Hern\u00e1ndez-Mendoza","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Din\u00e1mica Celular, Instituto de Investigaci\u00f3n en Ciencias B\u00e1sicas y Aplicadas, Universidad Aut\u00f3noma del Estado de Morelos, Chamilpa, Cuernavaca 62209, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Mart\u00ednez-Acu\u00f1a","sequence":"additional","affiliation":[{"name":"Facultad de Medicina Mexicali, Universidad Aut\u00f3noma de Baja California, Centro C\u00edvico, Mexicali 21000, Baja California, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2311-2534","authenticated-orcid":false,"given":"Ana Mar\u00eda","family":"Rivas-Estilla","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Medicina Molecular, Facultad de Medicina y Hospital Universitario \u201cDr. Jos\u00e9 Eleuterio Gonz\u00e1lez\u201d, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Av. Francisco I. Madero s\/n y Dr. Eduardo Aguirre Peque\u00f1o, Mitras Centro, Monterrey 64460, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Gerardo","family":"Gonz\u00e1lez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, Facultad de Medicina y Hospital Universitario \u201cDr. Jos\u00e9 Eleuterio Gonz\u00e1lez\u201d, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Mitras Centro, Monterrey 64460, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7305-6676","authenticated-orcid":false,"given":"Mar\u00eda Carmen","family":"Barboza-Cerda","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Medicina Molecular, Facultad de Medicina y Hospital Universitario \u201cDr. Jos\u00e9 Eleuterio Gonz\u00e1lez\u201d, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Av. Francisco I. Madero s\/n y Dr. Eduardo Aguirre Peque\u00f1o, Mitras Centro, Monterrey 64460, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Ibarra, A., Mart\u00ednez-Razo, L.D., V\u00e1zquez-Mart\u00ednez, E.R., Mart\u00ednez-Cruz, N., Flores-Ram\u00edrez, R., Garc\u00eda-G\u00f3mez, E., L\u00f3pez-L\u00f3pez, M., Ortega-Gonz\u00e1lez, C., Camacho-Arroyo, I., and Cerb\u00f3n, M. (2019). Unhealthy Levels of Phthalates and Bisphenol A in Mexican Pregnant Women with Gestational Diabetes and Its Association to Altered Expression of miRNAs Involved with Metabolic Disease. Int. J. Mol. 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