{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T07:06:57Z","timestamp":1790492817727,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011773","name":"Conseil R\u00e9gional de Bourgogne","doi-asserted-by":"publisher","award":["OBEDI"],"award-info":[{"award-number":["OBEDI"]}],"id":[{"id":"10.13039\/501100011773","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Maternal obesity is associated with a wide spectrum of labour disorders, including preterm birth. Leptin, a pro-inflammatory adipokine and a key factor of obesity, is suspected to play a major role in these disorders. OB-R, its receptor, is expressed on macrophages and myocytes, two cell types critical for labour onset. Macrophages secrete reactive oxygen species\/pro-inflammatory cytokines, responsible for myometrial differentiation while myocytes control uterine contractions. In this study, we assessed the effect of leptin on myometrial contraction and differentiation using our validated co-culture model of human primary macrophages and myocytes. We demonstrated that leptin had a different effect on myocytes and macrophages depending on the dose. A low leptin concentration induced a tocolytic effect by preventing myocytes\u2019 contraction, differentiation, and macrophage-induced ROS production. Additionally, leptin led to an increase in HLA-G expression, suggesting that the tocolytic effect of leptin may be driven by HLA-G, a tolerogenic molecule. Finally, we observed that recombinant HLA-G also prevented LPS-induced ROS production by macrophages. Altogether, these data provide a putative molecular mechanism by which leptin may induce immune tolerance and therefore interfere with labour-associated mechanisms. Therefore, HLA-G represents a potential innovative therapeutic target in the pharmacological management of preterm labour.<\/jats:p>","DOI":"10.3390\/cells11060954","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T11:46:47Z","timestamp":1646912807000},"page":"954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9532-5702","authenticated-orcid":false,"given":"Maeva","family":"Wendremaire","sequence":"first","affiliation":[{"name":"UMR 1231, Lipides Nutrition Cancer, INSERM, F-21000 Dijon, France"},{"name":"UFR des Sciences de Sant\u00e9, Universit\u00e9 Bourgogne Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana E.","family":"Lopez","sequence":"additional","affiliation":[{"name":"UMR 1231, Lipides Nutrition Cancer, INSERM, F-21000 Dijon, France"},{"name":"UFR des Sciences de Sant\u00e9, Universit\u00e9 Bourgogne Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Barrichon","sequence":"additional","affiliation":[{"name":"UMR 1231, Lipides Nutrition Cancer, INSERM, F-21000 Dijon, France"},{"name":"UFR des Sciences de Sant\u00e9, Universit\u00e9 Bourgogne Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Zhang","sequence":"additional","affiliation":[{"name":"UMR 1231, Lipides Nutrition Cancer, INSERM, F-21000 Dijon, France"},{"name":"UFR des Sciences de Sant\u00e9, Universit\u00e9 Bourgogne Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"},{"name":"School of Basic Medical Science, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarik","family":"Hadi","sequence":"additional","affiliation":[{"name":"UMR 1231, Lipides Nutrition Cancer, INSERM, F-21000 Dijon, France"},{"name":"UFR des Sciences de Sant\u00e9, Universit\u00e9 Bourgogne Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3739-0930","authenticated-orcid":false,"given":"Xiang-Yang","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Neiers","sequence":"additional","affiliation":[{"name":"UFR des Sciences de Sant\u00e9, Universit\u00e9 Bourgogne Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"},{"name":"Centre des Sciences du Go\u00fbt et de l\u2019Alimentation, INRAE, CNRS, Universit\u00e9 Bourgogne Franche-Comt\u00e9, F-21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0028-1837","authenticated-orcid":false,"given":"Marc","family":"Bardou","sequence":"additional","affiliation":[{"name":"UFR des Sciences de Sant\u00e9, Universit\u00e9 Bourgogne Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"},{"name":"CIC 1432, INSERM, Universit\u00e9 de Bourgogne Franche-Comt\u00e9, F-21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Sagot","sequence":"additional","affiliation":[{"name":"Service de Gyn\u00e9cologie-Obst\u00e9trique, Centre Hospitalo-Universitaire Dijon, F-21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Garrido","sequence":"additional","affiliation":[{"name":"UMR 1231, Lipides Nutrition Cancer, INSERM, F-21000 Dijon, France"},{"name":"UFR des Sciences de Sant\u00e9, Universit\u00e9 Bourgogne Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"},{"name":"Department of Medical Oncology, Centre Georges Fran\u00e7ois Leclerc, F-21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Lirussi","sequence":"additional","affiliation":[{"name":"UMR 1231, Lipides Nutrition Cancer, INSERM, F-21000 Dijon, France"},{"name":"UFR des Sciences de Sant\u00e9, Universit\u00e9 Bourgogne Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"},{"name":"Plateforme PACE, Laboratoire de Pharmacologie-Toxicologie, Centre Hospitalo-Universitaire Besan\u00e7on, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S120","DOI":"10.1038\/ijo.2008.247","article-title":"WHO Recognition of the Global Obesity Epidemic","volume":"32","author":"James","year":"2008","journal-title":"Int. J. Obes."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1001\/jama.2016.6458","article-title":"Trends in Obesity Among Adults in the USA, 2005 to 2014","volume":"315","author":"Flegal","year":"2016","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/S2213-8587(16)30217-0","article-title":"Preconceptional and Maternal Obesity: Epidemiology and Health Consequences","volume":"4","author":"Poston","year":"2016","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e020717","DOI":"10.1161\/JAHA.120.020717","article-title":"Trends in Prepregnancy Obesity and Association with Adverse Pregnancy Outcomes in the USA, 2013 to 2018","volume":"10","author":"Wang","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1001\/jama.2013.6295","article-title":"Maternal Obesity and Risk of Preterm Delivery","volume":"309","author":"Cnattingius","year":"2013","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"428.e1","DOI":"10.1016\/j.ajog.2013.12.011","article-title":"Association of Extremes of Prepregnancy BMI with the Clinical Presentations of Preterm Birth","volume":"210","author":"Lynch","year":"2014","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"19863","DOI":"10.1038\/s41598-021-98892-y","article-title":"Effects of Pre-Pregnancy Body Mass Index on Pregnancy and Perinatal Outcomes in Women Based on a Retrospective Cohort","volume":"11","author":"Xie","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1111\/j.1471-0528.2010.02889.x","article-title":"Maternal Obesity and Labour Complications Following Induction of Labour in Prolonged Pregnancy","volume":"118","author":"Arrowsmith","year":"2011","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1055\/s-0037-1605574","article-title":"Spontaneous Labor Onset and Outcomes in Obese Women at Term","volume":"35","author":"Frolova","year":"2018","journal-title":"Am. J. Perinatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1111\/aogs.14017","article-title":"Maternal Body Mass Index and Risk of Obstetric, Maternal and Neonatal Outcomes: A Cohort Study of Nulliparous Women with Spontaneous Onset of Labor","volume":"100","author":"Dalbye","year":"2021","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1079\/PNS2004406","article-title":"The Biology of Obesity","volume":"64","author":"Trayhurn","year":"2005","journal-title":"Proc. Nutr. Soc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1146\/annurev.physiol.62.1.413","article-title":"Leptin","volume":"62","author":"Ahima","year":"2000","journal-title":"Annu. Rev. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1056\/NEJM199602013340503","article-title":"Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans","volume":"334","author":"Considine","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.physbeh.2006.05.038","article-title":"The Role of Leptin in Leptin Resistance and Obesity","volume":"88","author":"Zhang","year":"2006","journal-title":"Physiol. Behav."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/oby.2010.172","article-title":"The Influence of Overweight and Obesity on Longitudinal Trends in Maternal Serum Leptin Levels during Pregnancy","volume":"19","author":"Misra","year":"2011","journal-title":"Obes. (Silver Spring Md.)"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4501","DOI":"10.1210\/endo.138.10.5573","article-title":"Synthesis of Leptin in Human Placenta","volume":"138","author":"Casabiell","year":"1997","journal-title":"Endocrinology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"363.e1","DOI":"10.1016\/j.ajog.2011.05.041","article-title":"Effects of Leptin on Lipopolysaccharide-Induced Myometrial Apoptosis in an in Vitro Human Model of Chorioamnionitis","volume":"205","author":"Wendremaire","year":"2011","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.placenta.2015.01.006","article-title":"Leptin Promotes HLA-G Expression on Placental Trophoblasts via the MEK\/Erk and PI3K Signaling Pathways","volume":"36","author":"Barrientos","year":"2015","journal-title":"Placenta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.gene.2016.07.014","article-title":"Maternal and Neonatal Leptin and Leptin Receptor Polymorphisms Associated with Preterm Birth","volume":"591","author":"Salem","year":"2016","journal-title":"Gene"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.ajog.2006.01.106","article-title":"Inhibitory Effect of Leptin on Human Uterine Contractility in Vitro","volume":"195","author":"Moynihan","year":"2006","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1095\/biolreprod.112.104844","article-title":"Effects of Leptin on Lipopolysaccharide-Induced Remodeling in an in Vitro Model of Human Myometrial Inflammation","volume":"88","author":"Wendremaire","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.1111\/bph.13100","article-title":"Dose-Dependent Biphasic Leptin-Induced Proliferation Is Caused by Non-Specific IL-6\/NF-\u039aB Pathway Activation in Human Myometrial Cells","volume":"172","author":"Barrichon","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1093\/humrep\/14.1.229","article-title":"Leukocytes Infiltrate the Myometrium during Human Parturition: Further Evidence That Labour Is an Inflammatory Process","volume":"14","author":"Thomson","year":"1999","journal-title":"Hum. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1095\/biolreprod.113.114975","article-title":"A New Role for Monocytes in Modulating Myometrial Inflammation during Human Labor","volume":"91","author":"Srikhajon","year":"2014","journal-title":"Biol. Reprod."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.1096\/fj.14-266783","article-title":"Glutathione Prevents Preterm Parturition and Fetal Death by Targeting Macrophage-Induced Reactive Oxygen Species Production in the Myometrium","volume":"29","author":"Hadi","year":"2015","journal-title":"FASEB J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1093\/biolre\/ioaa032","article-title":"Macrophage-Induced Reactive Oxygen Species Promote Myometrial Contraction and Labor-Associated Mechanisms","volume":"102","author":"Wendremaire","year":"2020","journal-title":"Biol. Reprod."},{"key":"ref_27","first-page":"e51554","article-title":"Isolation of Human Monocytes by Double Gradient Centrifugation and Their Differentiation to Macrophages in Teflon-Coated Cell Culture Bags","volume":"91","author":"Menck","year":"2014","journal-title":"J. Vis. Exp. JoVE"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"R12","DOI":"10.1186\/gb-2005-6-2-r12","article-title":"Identifying Genetic Networks Underlying Myometrial Transition to Labor","volume":"6","author":"Salomonis","year":"2005","journal-title":"Genome Biol."},{"key":"ref_29","first-page":"422","article-title":"Scrape-Loading and Dye Transfer. A Rapid and Simple Technique to Study Gap Junctional Intercellular Communication","volume":"168","author":"Trosko","year":"1987","journal-title":"Exp. Cell Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S0891-5849(00)00336-1","article-title":"Detection of Superoxide Anion Released Extracellularly by Endothelial Cells Using Cytochrome C Reduction, ESR, Fluorescence and Lucigenin-Enhanced Chemiluminescence Techniques","volume":"29","author":"Barbacanne","year":"2000","journal-title":"Free Radic. Biol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.ajpath.2011.04.024","article-title":"Complement Activation Triggers Metalloproteinases Release Inducing Cervical Remodeling and Preterm Birth in Mice","volume":"179","author":"Gonzalez","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1093\/molehr\/gav074","article-title":"Oxidative Stress Damage-Associated Molecular Signaling Pathways Differentiate Spontaneous Preterm Birth and Preterm Premature Rupture of the Membranes","volume":"22","author":"Dutta","year":"2016","journal-title":"Mol. Hum. Reprod."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.mehy.2009.07.039","article-title":"Leptin--a Tocolytic Agent for the Future?","volume":"74","author":"Wuntakal","year":"2010","journal-title":"Med. Hypotheses"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"103050","DOI":"10.1016\/j.amsu.2021.103050","article-title":"Maternal and Fetal Serum Leptin Levels and Their Association with Maternal and Fetal Variables and Labor: A Cross-Sectional Study","volume":"72","author":"Obeidat","year":"2021","journal-title":"Ann. Med. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1507\/endocrj.51.177","article-title":"Significant Increase in Maternal Plasma Leptin Concentration in Induced Delivery: A Possible Contribution of pro-Inflammatory Cytokines to Placental Leptin Secretion","volume":"51","author":"Nuamah","year":"2004","journal-title":"Endocr. J."},{"key":"ref_36","first-page":"569","article-title":"The Role of Nuclear Factor Kappa B in Human Labour","volume":"130","author":"Bennett","year":"2005","journal-title":"Reprod. Camb. Engl."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S90","DOI":"10.1016\/j.placenta.2008.10.005","article-title":"Transcriptional Regulation of the Processes of Human Labour and Delivery","volume":"30","author":"Lappas","year":"2009","journal-title":"Placenta"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-P\u00e9rez, A., S\u00e1nchez-Jim\u00e9nez, F., Vilari\u00f1o-Garc\u00eda, T., and S\u00e1nchez-Margalet, V. (2020). Role of Leptin in Inflammation and Vice Versa. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165887"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3122","DOI":"10.4049\/jimmunol.2001152","article-title":"Leptin Augments Antitumor Immunity in Obesity by Repolarizing Tumor-Associated Macrophages","volume":"207","author":"Dudzinski","year":"2021","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/carcin\/bgl137","article-title":"Leptin Induces an Apc Genotype-Associated Colon Epithelial Cell Chemokine Production Pattern Associated with Macrophage Chemotaxis and Activation","volume":"28","author":"Fenton","year":"2007","journal-title":"Carcinogenesis"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5564","DOI":"10.1158\/1078-0432.CCR-12-3697","article-title":"Molecular Pathways: Human Leukocyte Antigen G (HLA-G)","volume":"19","author":"Curigliano","year":"2013","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"447.e7","DOI":"10.1016\/j.ajog.2012.03.013","article-title":"A Novel Bridge between Oxidative Stress and Immunity: The Interaction between Hydrogen Peroxide and Human Leukocyte Antigen G in Placental Trophoblasts during Preeclampsia","volume":"206","author":"Zhou","year":"2012","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1111\/j.1471-0528.2009.02453.x","article-title":"Different Profiles of Circulating Angiogenic Factors and Adipocytokines between Early- and Late-Onset Pre-Eclampsia","volume":"117","author":"Masuyama","year":"2010","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1093\/humrep\/dev196","article-title":"Soluble Human Leukocyte Antigen G5 Polarizes Differentiation of Macrophages toward a Decidual Macrophage-like Phenotype","volume":"30","author":"Lee","year":"2015","journal-title":"Hum. Reprod. Oxf. Engl."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"592010","DOI":"10.3389\/fimmu.2020.592010","article-title":"Roles of HLA-G in the Maternal-Fetal Immune Microenvironment","volume":"11","author":"Xu","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1600-0897.2007.00475.x","article-title":"Early Detection of Decreased Soluble HLA-G Levels in the Maternal Circulation Predicts the Occurrence of Preeclampsia and Intrauterine Growth Retardation during Further Course of Pregnancy","volume":"57","author":"Steinborn","year":"2007","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jri.2016.11.005","article-title":"Soluble HLA-G Concentrations in Obese Women during Pregnancy and in Cord Blood","volume":"119","author":"Beneventi","year":"2017","journal-title":"J. Reprod. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1093\/molehr\/gav027","article-title":"Crosstalk between Monocytes and Myometrial Smooth Muscle in Culture Generates Synergistic Pro-Inflammatory Cytokine Production and Enhances Myocyte Contraction, with Effects Opposed by Progesterone","volume":"21","author":"Rajagopal","year":"2015","journal-title":"Mol. Hum. Reprod."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Boros-Rausch, A., Shynlova, O., and Lye, S.J. (2021). A Broad-Spectrum Chemokine Inhibitor Blocks Inflammation-Induced Myometrial Myocyte-Macrophage Crosstalk and Myometrial Contraction. 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