{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T16:45:18Z","timestamp":1794588318569,"version":"4.9.1"},"reference-count":68,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T00:00:00Z","timestamp":1762646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo a Pesquisa do Estado de Mato Grosso","award":["000253\/2023"],"award-info":[{"award-number":["000253\/2023"]}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brazil","doi-asserted-by":"crossref","award":["CAPES\u2014Finance Code 001"],"award-info":[{"award-number":["CAPES\u2014Finance Code 001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","award":["312511\/2023-0"],"award-info":[{"award-number":["312511\/2023-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","award":["312841\/2023-0"],"award-info":[{"award-number":["312841\/2023-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gestational Diabetes Mellitus (GDM) is a metabolic condition characterized by glucose intolerance, which manifests or is diagnosed for the first time during pregnancy. Hyperglycemia associated with GDM can induce a systemic and local inflammatory environment, directly affecting the maternal\u2013fetal interface, particularly the placenta. The placenta, in turn, plays a central role in immune modulation and can alter cytokine and immune cell expression in response to metabolic stress. This study aimed to evaluate levels of inflammatory cytokines and the profiles of type 1 (M1) and type 2 (M2) macrophages in placentas from pregnant women with GDM. Forty placental samples were analyzed and divided into two groups: pregnant women with GDM (n = 20) and normoglycemic pregnant women (n = 20). The villous and extravillous portions were separated and analyzed for cytokine levels by flow cytometry and for macrophage immunophenotyping. The results showed a significant increase in IL-6, IL-8, IL-10, and IL-12P70 levels in the placentas of mothers with GDM, whereas IL-1\u03b2 and TNF-\u03b1 were reduced in the extravillous portion of this group. In addition, a higher percentage of CD14+ cells and M2 macrophages was observed, especially in the villous portion of the placentas of pregnant women with GDM. These findings suggest that gestational hyperglycemia modulates the placental immune response, altering cytokine levels and macrophage polarization patterns. GDM influences the placental immunological microenvironment, which can contribute to alterations in placental function and increased risks to fetal development. The data underscore the placenta\u2019s role as an immunoregulatory organ and highlight the need for greater attention to inflammation associated with GDM in maternal and child health.<\/jats:p>","DOI":"10.3390\/ijms262210867","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T08:57:55Z","timestamp":1762765075000},"page":"10867","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Gestational Diabetes Mellitus Alters Cytokine Profiles and Macrophage Polarization in Human Placenta"],"prefix":"10.3390","volume":"26","author":[{"given":"Martalice Ribeiro","family":"Barbosa","sequence":"first","affiliation":[{"name":"Postgraduate Program in Basic and Applied Immunology and Parasitology, Federal University of Mato Grosso, Barra do Gar\u00e7as 78600-000, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Feres de","family":"Marchi","sequence":"additional","affiliation":[{"name":"Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Gar\u00e7as 78600-000, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00eania Maria Rezende","family":"Silva","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Basic and Applied Immunology and Parasitology, Federal University of Mato Grosso, Barra do Gar\u00e7as 78600-000, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4921-4064","authenticated-orcid":false,"given":"Danielle Cristina Honorio","family":"Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Basic and Applied Immunology and Parasitology, Federal University of Mato Grosso, Barra do Gar\u00e7as 78600-000, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcondes Alves Barbosa da","family":"Silva","sequence":"additional","affiliation":[{"name":"Institute of Health Science, Federal University of Rondon\u00f3polis, Rondon\u00f3polis 78736-900, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6238-7173","authenticated-orcid":false,"given":"Jakeline","family":"Ribeiro Barbosa","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz\u2014Fiocruz, Bras\u00edlia 70904-970, DF, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Valdiane Luz","family":"Melo","sequence":"additional","affiliation":[{"name":"Institute of Health Science, Federal University of Rondon\u00f3polis, Rondon\u00f3polis 78736-900, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1854-5397","authenticated-orcid":false,"given":"Eduardo Luz\u00eda","family":"Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Basic and Applied Immunology and Parasitology, Federal University of Mato Grosso, Barra do Gar\u00e7as 78600-000, MT, Brazil"},{"name":"Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Gar\u00e7as 78600-000, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0452-9804","authenticated-orcid":false,"given":"Adenilda Cristina","family":"Honorio-Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Basic and Applied Immunology and Parasitology, Federal University of Mato Grosso, Barra do Gar\u00e7as 78600-000, MT, Brazil"},{"name":"Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Gar\u00e7as 78600-000, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1210\/endrev\/bnac003","article-title":"A clinical update on gestational diabetes mellitus","volume":"43","author":"Stetting","year":"2022","journal-title":"Endocr. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s11892-015-0699-x","article-title":"Prevalence of gestational diabetes and risk of progression to type 2 diabetes: A global perspective","volume":"16","author":"Zhu","year":"2016","journal-title":"Curr. Diabetes Rep."},{"key":"ref_3","first-page":"213","article-title":"Perinatal complications associated with pregestational and gestational diabetes","volume":"29","author":"Mitanchez","year":"2015","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7154524","DOI":"10.1155\/2016\/7154524","article-title":"Characterization of natural killer cells and cytokines in maternal placenta and fetus of diabetic mothers","volume":"2016","author":"Hara","year":"2016","journal-title":"J. Immunol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/apm.12772","article-title":"The modulatory role of cytokines IL-4 and IL-17 in the functional activity of phagocytes in diabetic pregnant women","volume":"126","author":"Fagundes","year":"2018","journal-title":"APMIS"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Tauber, Z., Burianova, A., Koubova, K., Mrstik, M., Jirkovska, M., and Cizkova, K. (2024). The interplay of inflammation and placenta in maternal diabetes: Insights into Hofbauer cell expression patterns. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1386528"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Cao, J., Jiang, W., Yin, Z., Li, N., Tong, C., and Qi, H. (2024). Mechanistic study of preeclampsia and macrophage-associated molecular networks: Bioinformatics insights from multiple datasets. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1376971"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bezemer, R.E., Faas, M., van Goor, H., Gordijn, S.J., and Prins, J. (2024). Decidual macrophages and Hofbauer cells in fetal growth restriction. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1379537"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Szukiewicz, D. (2024). Insights into reproductive immunology and placental lipid\u2013cytokine interplay in macrosomia: A narrative review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212135"},{"key":"ref_10","first-page":"21","article-title":"Macrophage function in normal and diabetic pregnancies","volume":"132","author":"Holder","year":"2019","journal-title":"J. Reprod. Immunol."},{"key":"ref_11","first-page":"13","article-title":"Placental histopathological findings in gestational diabetes mellitus","volume":"98","author":"Cobo","year":"2020","journal-title":"Placenta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e13509","DOI":"10.1111\/aji.13509","article-title":"Effects of anti-beta 2-glycoprotein 1 antibodies and its association with pregnancy-related morbidity in antiphospholipid syndrome","volume":"87","author":"Fierro","year":"2022","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3479","DOI":"10.1007\/s00018-019-03104-6","article-title":"Human placenta and trophoblast development: Key molecular mechanisms and model systems","volume":"76","author":"Haider","year":"2019","journal-title":"Cell Mol. Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Olmos-Ortiz, A., Flores-Espinosa, P., D\u00edaz, L., Vel\u00e1zquez, P., Ram\u00edrez-Isarraraz, C., and Zaga-Clavellina, V. (2021). Immunoendocrine Dysregulation during Gestational Diabetes Mellitus: The Central Role of the Placenta. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158087"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yang, Y., Guo, F., Peng, Y., Chen, R., Zhou, W., Wang, H., OuYang, J., Yu, B., and Xu, Z. (2021). Transcriptomic profiling of human placenta in gestational diabetes mellitus at the single-cell level. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.679582"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cui, S.S., Zhang, P., Sun, L., Yuan, Y.L.L., Wang, J., Zhang, F.X., and Li, R. (2023). Mucin1 induced trophoblast dysfunction in gestational diabetes mellitus via Wnt\/\u03b2-catenin signaling pathway. Biol. Res., 56.","DOI":"10.1186\/s40659-023-00460-3"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhang, Y.N., Wu, Q., and Deng, Y.H. (2024). Phenotypic characterisation of regulatory T cells in patients with gestational diabetes mellitus. Sci. Rep., 14.","DOI":"10.1038\/s41598-023-47638-z"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zgutka, K., Tkacz, M., Tomasiak, P., Piotrowska, K., Ustianowski, P., Pawlik, A., and Tarnowski, M. (2024). Gestational diabetes mellitus-induced inflammation in the placenta via IL-1\u03b2 and Toll-like receptor pathways. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111409"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Schliefsteiner, C., Peinhaupt, M., Kopp, S., L\u00f6gl, J., Lang-Olip, I., Hiden, U., Heinemann, A., Desoye, G., and Wadsack, C. (2017). Human placental Hofbauer cells maintain an anti-inflammatory M2 phenotype despite the presence of gestational diabetes mellitus. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00888"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Fran\u00e7a, D.C.H., Honorio-Fran\u00e7a, A.C., Silva, K.M.R., Alves, F.C.B., Bueno, G., Costa, S.M.B., Cotrim, A.C.D.M., Barbosa, A.M.P., Fran\u00e7a, E.L., and Rudge, M.V.C. (2023). Serotonin and interleukin 10 can influence the blood and urine viscosity in gestational diabetes mellitus and pregnancy-specific urinary incontinence. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417125"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Fran\u00e7a, D.C.H., Fran\u00e7a, E.L., Sobrevia, L., Barbosa, A.M.P., and Ho, A.C. (2023). Integration of nutrigenomics, melatonin, serotonin and inflammatory cytokines in the pathophysiology of pregnancy-specific urinary incontinence in women with gestational diabetes mellitus. Front. Med., 10.","DOI":"10.1016\/j.bbadis.2023.166737"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhang, Y.H., He, M., Wang, Y., and Liao, A.H. (2017). Modulators of the balance between M1 and M2 macrophages during pregnancy. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00120"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sharma, S., Banerjee, S., Krueger, P.M., and Blois, S.M. (2021). Immunobiology of gestational diabetes mellitus in post-Medawar era. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.758267"},{"key":"ref_24","first-page":"56","article-title":"The distributional characteristics of M2 macrophages in the placental chorionic villi are altered among term pregnant women with uncontrolled type 2 diabetes mellitus","volume":"120","author":"Zhang","year":"2022","journal-title":"Placenta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"727","DOI":"10.4103\/ijpm.ijpm_99_22","article-title":"CD68 expression in the placenta of gestational diabetic mothers: A case-control study","volume":"66","author":"Gosain","year":"2023","journal-title":"Indian J. Pathol. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Silva, K.M.R., Fran\u00e7a, D.C.H., de Queiroz, A.A., Fagundes-Triches, D.L.G., de Marchi, P.G.F., Morais, T.C., Honorio-Fran\u00e7a, A.C., and Fran\u00e7a, E.L. (2023). Polarization of melatonin-modulated colostrum macrophages in the presence of breast tumor cell lines. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512400"},{"key":"ref_27","unstructured":"American Diabetes Association (2025). Standards of Care in Diabetes. Diabetes Care, 48, S1\u2013S352."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1002\/bdr2.1135","article-title":"Hypoxia and placental development","volume":"109","author":"Soares","year":"2017","journal-title":"Birth Defects Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.placenta.2005.08.009","article-title":"The placenta cytokine network and inflammatory signals","volume":"27","year":"2006","journal-title":"Placenta"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.diabres.2015.01.005","article-title":"Changes in the TNF-alpha\/IL-10 ratio in hyperglycemia-associated pregnancies","volume":"107","author":"Moreli","year":"2015","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Mandal\u00e0, M. (2025). Oxidative Stress and Inflammation in Uterine\u2013Vascular Adaptation During Pregnancy. Antioxidants, 14.","DOI":"10.3390\/antiox14091051"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Plows, J.F., Stanley, J.L., Baker, P.N., Reynolds, C.M., and Vickers, M.H. (2018). The pathophysiology of gestational diabetes mellitus. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113342"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.2337\/diabetes.52.12.2951","article-title":"Gestational diabetes induces placental genes for chronic stress and inflammatory pathways","volume":"52","author":"Radaelli","year":"2003","journal-title":"Diabetes"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1152\/physrev.00029.2015","article-title":"Placental origins of chronic disease","volume":"96","author":"Burton","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Colombini, A., Libonati, F., Cangelosi, D., Lopa, S., De Luca, P., Coviello, D.A., Moretti, M., and de Girolamo, L. (2022). Inflammatory priming with IL-1\u03b2 promotes the immunomodulatory behavior of adipose derived stem cells. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.1000879"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8171","DOI":"10.1007\/s11033-021-06785-0","article-title":"GDM-complicated pregnancies: Focus on adipokines","volume":"48","author":"Mallardo","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.immuni.2018.07.017","article-title":"Interferons and proinflammatory cytokines in pregnancy and fetal development","volume":"49","author":"Yockey","year":"2018","journal-title":"Immunity"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wu, R.Y., Xiao, K., Hotte, N., Tandon, P., Elloumi, Y., Ambrosio, L., Dunsmore, G., Elahi, S., Kroeker, K.I., and Dieleman, L.A. (2022). Elevated IL-6 and IL-22 in Early Pregnancy Are Associated with Worse Disease Course in Women with Inflammatory Bowel Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810281"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Viloti\u0107, A., Nacka-Aleksi\u0107, M., Pirkovi\u0107, A., Boji\u0107-Trbojevi\u0107, \u017d., Dekanski, D., and Jovanovi\u0107 Krivoku\u0107a, M. (2022). IL-6 and IL-8: An Overview of Their Roles in Healthy and Pathological Pregnancies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314574"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Murthi, P., Pinar, A.A., Dimitriadis, E., and Samuel, C.S. (2020). Inflammasomes\u2014A Molecular Link for Altered Immunoregulation and Inflammation Mediated Vascular Dysfunction in Preeclampsia. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041406"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1080\/08820130802191375","article-title":"The role of macrophages in utero-placental interactions during normal and pathological pregnancy","volume":"37","author":"Renaud","year":"2008","journal-title":"Immunol. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Abu-Raya, B., Michalski, C., Sadarangani, M., and Lavoie, P.M. (2020). Maternal immunological adaptation during normal pregnancy. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.575197"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kang, J., Lee, C.-N., Li, H.-Y., Hsu, K.-H., Wang, S.-H., and Lin, S.-Y. (2018). Association of interleukin-10 methylation levels with gestational diabetes in a Taiwanese population. Front. Genet., 9.","DOI":"10.3389\/fgene.2018.00222"},{"key":"ref_44","first-page":"928187","article-title":"Transfer of maternal immunity to newborns of diabetic mothers","volume":"2012","author":"Calderon","year":"2012","journal-title":"Clin. Dev. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"590190","DOI":"10.1155\/2013\/590190","article-title":"The role of cytokines in the functional activity of phagocytes in blood and colostrum of diabetic mothers","volume":"2013","author":"Fagundes","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"998","DOI":"10.3109\/14767058.2015.1031739","article-title":"Changes in T-cell phenotype and cytokines profile in maternal blood, cord blood and colostrum of diabetic mothers","volume":"29","author":"Fagundes","year":"2016","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Paparini, D.E., Grasso, E., Aguilera, F., Arslanian, M.A., Lella, V., Lara, B., Schafir, A., Gori, S., Merech, F., and Hauk, V. (2024). Sex-specific phenotypical, functional and metabolic profiles of human term placenta macrophages. Biol. Sex Differ., 15.","DOI":"10.1186\/s13293-024-00652-w"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9","DOI":"10.5468\/ogs.24247","article-title":"The role of placenta Hofbauer cells during pregnancy and pregnancy complications","volume":"68","author":"Yang","year":"2025","journal-title":"Obstet. Gynecol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/sji.12466","article-title":"Maternal-foetal diabetes modifies neonatal Fc receptor expression on human leucocytes","volume":"84","author":"Souza","year":"2016","journal-title":"Scand. J. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Yao, Y., Xu, X.H., and Jin, L. (2019). Macrophage polarization in physiological and pathological pregnancy. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00792"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.1749-6632.2010.05938.x","article-title":"Inflammation and pregnancy: The role of the immune system at the implantation site","volume":"1221","author":"Mor","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/aji.12357","article-title":"The role of macrophages in promoting and maintaining homeostasis at the fetal-maternal interface","volume":"74","author":"Ernerudh","year":"2015","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ross, E.A., Devitt, A., and Johnson, J.R. (2021). Macrophages: The good, the bad, and the gluttony. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.708186"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"157041","DOI":"10.1016\/j.cyto.2025.157041","article-title":"Role of macrophage reprogramming in the pathogenesis of gestational diabetes mellitus","volume":"196","author":"Milan","year":"2025","journal-title":"Cytokine"},{"key":"ref_55","first-page":"178","article-title":"Macrophage plasticity and placental remodeling in pregnancy disorders","volume":"82","author":"Wei","year":"2025","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Mittal, R., Goyal, S., and Singh, D. (2025). Unveiling gestational diabetes: An overview of pathophysiology and clinical consequences. Front. Physiol., 16.","DOI":"10.3390\/ijms26052320"},{"key":"ref_57","unstructured":"Milan, K.L., Fang, R., and Zhao, T. (2025). Hyperglycemia-induced placental macrophage dysregulation in gestational diabetes mellitus. Front. Immunol., 16."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Szarka, A., Rig\u00f3, J., L\u00e1z\u00e1r, L., Beko, G., and Molvarec, A. (2010). Circulating cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia determined by multiplex suspension array. BMC Immunol., 11.","DOI":"10.1186\/1471-2172-11-59"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Luo, M., Zhao, F., Cheng, H., Su, M., and Wang, Y. (2024). Macrophage polarization: An important role in inflammatory diseases. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1352946"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.placenta.2015.05.016","article-title":"Aberrant maternal inflammation as a cause of pregnancy complications: A potential therapeutic target?","volume":"36","author":"Cotechini","year":"2015","journal-title":"Placenta"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e13020","DOI":"10.1111\/aji.13020","article-title":"Gestational diabetes mellitus is associated with increased CD163 expression and iron storage in the placenta","volume":"80","author":"Barke","year":"2018","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Louis, M.B.P., Fran\u00e7a, D.C.H., Queiroz, A.A., Calderon, I.M.P., Fran\u00e7a, E.L., and Honorio-Fran\u00e7a, A.C. (2022). Melatonin hormone acts on cells of maternal blood and placenta from diabetic mothers. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.765928"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1159\/000010293","article-title":"Perinatal outcome of pregnancies complicated by diabetes and by maternal daily hyperglycemia not related to diabetes: A retrospective 10-year analysis","volume":"50","author":"Rudge","year":"2000","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.diabres.2007.01.023","article-title":"Morphometric study of placental villi and vessels in women with mild hyperglycemia or gestational or overt diabetes","volume":"78","author":"Calderon","year":"2007","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_65","first-page":"193","article-title":"Regulation of MT1-MMP\/MMP-2\/TIMP-2 axis in human placenta","volume":"8","author":"Vincent","year":"2015","journal-title":"J. Inflamm. Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Fujimori, M., Fran\u00e7a, E.L., Fiorin, V., Morais, T.C., Honorio-Fran\u00e7a, A.C., and de Abreu, L.C. (2015). Changes in the biochemical and immunological components of serum and colostrum of overweight and obese mothers. BMC Pregnancy Childbirth, 15.","DOI":"10.1186\/s12884-015-0574-4"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Borbely, A.U., Sandri, S., Fernandes, I.R., Prado, K.M., Cardoso, E.C., Correa-Silva, S., Albuquerque, R., Kn\u00f6fler, M., Beltr\u00e3o-Braga, P., and Campa, A. (2014). The term basal plate of the human placenta as a source of functional extravillous trophoblast cells. Reprod. Biol. Endocrinol., 12.","DOI":"10.1186\/1477-7827-12-7"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/ijms21155497","article-title":"Targeting of CD163+ macrophages in inflammatory and malignant diseases","volume":"21","author":"Skytthe","year":"2020","journal-title":"Int. J. Mol. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/22\/10867\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T05:24:16Z","timestamp":1762838656000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/22\/10867"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,9]]},"references-count":68,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262210867"],"URL":"https:\/\/doi.org\/10.3390\/ijms262210867","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,9]]}}}