Decreased number of myeloid-derived suppressor cells in the placental trophoblast of gestational diabetes mellitus. Possible role of leptin

Gestational diabetes mellitus (GDM) is the most common complication of pregnancy and significantly increases both maternal and fetal morbidity and mortality. Inflammation is a hallmark of GDM, and placental inflammation may play a key role in the pathophysiology of the disease. Myeloid-derived suppr...

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Autores: Tami, Malika, Hontecillas-Prieto, Lourdes, García-Domínguez, Daniel, Flores-Campos, Rocío, Vilariño-García, Teresa, Sánchez-Jiménez, Flora, Guadix, Pilar, Dueñas, José L, Jiménez-Cortegana, Carlos, Cruz-Merino, Luis de la, Pérez-Pérez, Antonio, Sánchez-Margalet, Víctor
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/390688
Acceso en línea:http://hdl.handle.net/10261/390688
https://api.elsevier.com/content/abstract/scopus_id/105000890733
Access Level:acceso abierto
Palabra clave:Gestational diabetes mellitus
Leptin
MDSC
Placenta
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spelling Decreased number of myeloid-derived suppressor cells in the placental trophoblast of gestational diabetes mellitus. Possible role of leptinTami, MalikaHontecillas-Prieto, LourdesGarcía-Domínguez, DanielFlores-Campos, RocíoVilariño-García, TeresaSánchez-Jiménez, FloraGuadix, PilarDueñas, José LJiménez-Cortegana, CarlosCruz-Merino, Luis de laPérez-Pérez, AntonioSánchez-Margalet, VíctorGestational diabetes mellitusLeptinMDSCPlacentaGestational diabetes mellitus (GDM) is the most common complication of pregnancy and significantly increases both maternal and fetal morbidity and mortality. Inflammation is a hallmark of GDM, and placental inflammation may play a key role in the pathophysiology of the disease. Myeloid-derived suppressor cells (MDSCs), which are innate immunosuppressive, are thought to contribute to feto-maternal tolerance. In normal pregnancies, elevated levels of MDSCs have been observed in both peripheral and umbilical cord blood. Our hypothesis postulates that trophoblasts from placentas belonging to women with GDM may have lower levels of MDSCs compared to trophoblasts from placentas originating from healthy pregnancies. Furthermore, since leptin is overexpressed in the placenta of GDM patients, we hypothesized that leptin might contribute to the reduction of MDSCs. To test this, we investigated the in vitro effects of leptin on MDSC levels in isolated peripheral blood leukocytes after 24 h of incubation. Our findings indicate that trophoblasts from placentas from women with GDM contain a lower percentage of MDSCs compared to trophoblasts from healthy pregnancies. In addition, in vitro studies demonstrated that leptin reduces the number of MDSCs in peripheral blood leukocytes. In conclusion, MDSCs are decreased in placentas from pregnancies with GDM, and leptin appears to reduce the number of MDSCs in leukocytes isolated in vitro. Increased leptin expression in trophoblasts from placentas of women with GDM may contribute to the lower levels of MDSCs, potentially playing a role in placental inflammation. However, further investigations are required to fully elucidate this mechanism.This research was funded by a grant from Instituto de Salud Carlos III (ISCIII) (PI19/01741), funded in part by FEDER Funds to VS-M. L.H-P. is supported by Miguel Servet research fellow at Instituto de Salud Carlos III. D.J.G-D. is supported by the VII Plan Propio de Investigación y Transferencia of Universidad de Sevilla [Contrato de Acceso (II.4)/VII PPIT-US].Peer reviewedElsevier BVInstituto de Salud Carlos IIIEuropean CommissionMinisterio de Ciencia, Innovación y Universidades (España)Universidad de SevillaGarcía-Domínguez, Daniel [0000-0001-8150-2747]Sánchez-Margalet, Víctor [0000-0001-8638-8680Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/390688https://api.elsevier.com/content/abstract/scopus_id/105000890733reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F01741The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1016/j.imbio.2025.152897https://doi.org/10.1016/j.imbio.2025.152897Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3906882026-05-22T06:33:51Z
dc.title.none.fl_str_mv Decreased number of myeloid-derived suppressor cells in the placental trophoblast of gestational diabetes mellitus. Possible role of leptin
title Decreased number of myeloid-derived suppressor cells in the placental trophoblast of gestational diabetes mellitus. Possible role of leptin
spellingShingle Decreased number of myeloid-derived suppressor cells in the placental trophoblast of gestational diabetes mellitus. Possible role of leptin
Tami, Malika
Gestational diabetes mellitus
Leptin
MDSC
Placenta
title_short Decreased number of myeloid-derived suppressor cells in the placental trophoblast of gestational diabetes mellitus. Possible role of leptin
title_full Decreased number of myeloid-derived suppressor cells in the placental trophoblast of gestational diabetes mellitus. Possible role of leptin
title_fullStr Decreased number of myeloid-derived suppressor cells in the placental trophoblast of gestational diabetes mellitus. Possible role of leptin
title_full_unstemmed Decreased number of myeloid-derived suppressor cells in the placental trophoblast of gestational diabetes mellitus. Possible role of leptin
title_sort Decreased number of myeloid-derived suppressor cells in the placental trophoblast of gestational diabetes mellitus. Possible role of leptin
dc.creator.none.fl_str_mv Tami, Malika
Hontecillas-Prieto, Lourdes
García-Domínguez, Daniel
Flores-Campos, Rocío
Vilariño-García, Teresa
Sánchez-Jiménez, Flora
Guadix, Pilar
Dueñas, José L
Jiménez-Cortegana, Carlos
Cruz-Merino, Luis de la
Pérez-Pérez, Antonio
Sánchez-Margalet, Víctor
author Tami, Malika
author_facet Tami, Malika
Hontecillas-Prieto, Lourdes
García-Domínguez, Daniel
Flores-Campos, Rocío
Vilariño-García, Teresa
Sánchez-Jiménez, Flora
Guadix, Pilar
Dueñas, José L
Jiménez-Cortegana, Carlos
Cruz-Merino, Luis de la
Pérez-Pérez, Antonio
Sánchez-Margalet, Víctor
author_role author
author2 Hontecillas-Prieto, Lourdes
García-Domínguez, Daniel
Flores-Campos, Rocío
Vilariño-García, Teresa
Sánchez-Jiménez, Flora
Guadix, Pilar
Dueñas, José L
Jiménez-Cortegana, Carlos
Cruz-Merino, Luis de la
Pérez-Pérez, Antonio
Sánchez-Margalet, Víctor
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
European Commission
Ministerio de Ciencia, Innovación y Universidades (España)
Universidad de Sevilla
García-Domínguez, Daniel [0000-0001-8150-2747]
Sánchez-Margalet, Víctor [0000-0001-8638-8680
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Gestational diabetes mellitus
Leptin
MDSC
Placenta
topic Gestational diabetes mellitus
Leptin
MDSC
Placenta
description Gestational diabetes mellitus (GDM) is the most common complication of pregnancy and significantly increases both maternal and fetal morbidity and mortality. Inflammation is a hallmark of GDM, and placental inflammation may play a key role in the pathophysiology of the disease. Myeloid-derived suppressor cells (MDSCs), which are innate immunosuppressive, are thought to contribute to feto-maternal tolerance. In normal pregnancies, elevated levels of MDSCs have been observed in both peripheral and umbilical cord blood. Our hypothesis postulates that trophoblasts from placentas belonging to women with GDM may have lower levels of MDSCs compared to trophoblasts from placentas originating from healthy pregnancies. Furthermore, since leptin is overexpressed in the placenta of GDM patients, we hypothesized that leptin might contribute to the reduction of MDSCs. To test this, we investigated the in vitro effects of leptin on MDSC levels in isolated peripheral blood leukocytes after 24 h of incubation. Our findings indicate that trophoblasts from placentas from women with GDM contain a lower percentage of MDSCs compared to trophoblasts from healthy pregnancies. In addition, in vitro studies demonstrated that leptin reduces the number of MDSCs in peripheral blood leukocytes. In conclusion, MDSCs are decreased in placentas from pregnancies with GDM, and leptin appears to reduce the number of MDSCs in leukocytes isolated in vitro. Increased leptin expression in trophoblasts from placentas of women with GDM may contribute to the lower levels of MDSCs, potentially playing a role in placental inflammation. However, further investigations are required to fully elucidate this mechanism.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/390688
https://api.elsevier.com/content/abstract/scopus_id/105000890733
url http://hdl.handle.net/10261/390688
https://api.elsevier.com/content/abstract/scopus_id/105000890733
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F01741
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1016/j.imbio.2025.152897
https://doi.org/10.1016/j.imbio.2025.152897
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier BV
publisher.none.fl_str_mv Elsevier BV
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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