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Volume 11
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10.3390/cells11060954
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Article

Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation

by
Maeva Wendremaire
1,2,
Tatiana E. Lopez
1,2,
Marina Barrichon
1,2,
Hang Zhang
1,2,3,
Tarik Hadi
1,2,
Xiang-Yang Ye
4,
Fabrice Neiers
2,5,
Marc Bardou
2,6,
Paul Sagot
7,
Carmen Garrido
1,2,8 and
Frédéric Lirussi
1,2,9,*
1
UMR 1231, Lipides Nutrition Cancer, INSERM, F-21000 Dijon, France
2
UFR des Sciences de Santé, Université Bourgogne Franche-Comté, F-25000 Besançon, France
3
School of Basic Medical Science, Hangzhou Normal University, Hangzhou 311121, China
4
School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China
5
Centre des Sciences du Goût et de l’Alimentation, INRAE, CNRS, Université Bourgogne Franche-Comté, F-21000 Dijon, France
6
CIC 1432, INSERM, Université de Bourgogne Franche-Comté, F-21000 Dijon, France
7
Service de Gynécologie-Obstétrique, Centre Hospitalo-Universitaire Dijon, F-21000 Dijon, France
8
Department of Medical Oncology, Centre Georges François Leclerc, F-21000 Dijon, France
9
Plateforme PACE, Laboratoire de Pharmacologie-Toxicologie, Centre Hospitalo-Universitaire Besançon, F-25000 Besançon, France
*
Author to whom correspondence should be addressed.
Cells 2022, 11(6), 954; https://doi.org/10.3390/cells11060954
Submission received: 31 January 2022 / Revised: 4 March 2022 / Accepted: 7 March 2022 / Published: 10 March 2022
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Abstract

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’ 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.
Keywords: leptin; differentiation; labour; macrophage; myometrium; oxidative stress leptin; differentiation; labour; macrophage; myometrium; oxidative stress

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MDPI and ACS Style

Wendremaire, M.; Lopez, T.E.; Barrichon, M.; Zhang, H.; Hadi, T.; Ye, X.-Y.; Neiers, F.; Bardou, M.; Sagot, P.; Garrido, C.; et al. Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation. Cells 2022, 11, 954. https://doi.org/10.3390/cells11060954

AMA Style

Wendremaire M, Lopez TE, Barrichon M, Zhang H, Hadi T, Ye X-Y, Neiers F, Bardou M, Sagot P, Garrido C, et al. Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation. Cells. 2022; 11(6):954. https://doi.org/10.3390/cells11060954

Chicago/Turabian Style

Wendremaire, Maeva, Tatiana E. Lopez, Marina Barrichon, Hang Zhang, Tarik Hadi, Xiang-Yang Ye, Fabrice Neiers, Marc Bardou, Paul Sagot, Carmen Garrido, and et al. 2022. "Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation" Cells 11, no. 6: 954. https://doi.org/10.3390/cells11060954

APA Style

Wendremaire, M., Lopez, T. E., Barrichon, M., Zhang, H., Hadi, T., Ye, X.-Y., Neiers, F., Bardou, M., Sagot, P., Garrido, C., & Lirussi, F. (2022). Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation. Cells, 11(6), 954. https://doi.org/10.3390/cells11060954

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