title: Effects of leptin on lipopolysaccharide-induced remodeling in an in vitro model of human myometrial inflammation.
abstract: Reorganization of myometrial extracellular matrix (ECM) is essential for the uterus to achieve powerful synchronous contractions during labor. Remodeling of the ECM has been implicated in membrane rupture and cervical ripening. Because maternal obesity is associated with both delivery disorders and elevated circulating leptin levels, this study aimed to assess the ability of leptin to interfere with lipopolysaccharide (LPS)-induced myometrial ECM remodeling. Myometrial biopsy samples were obtained from women undergoing cesarean delivery before labor onset. Myometrial explants were incubated for 48 h with LPS and leptin. LPS challenge was associated with a marked decrease in collagen content and in heat shock protein (HSP) 47 expression, reflecting a disruption in collagen synthesis and an increase in matrix metalloproteinase (MMP) 2 and MMP9 activity and in MMP2, MMP9, and MMP13 expression. Leptin prevented an LPS-induced decrease in myometrial collagen content in a concentration-dependent manner. This effect was associated with an increase in HSP47 expression and a decrease in MMP2 and MMP9 activity and expression. These results show that leptin prevents LPS-induced myometrial remodeling through collagen synthesis stimulation and inhibition of MMP2 and MMP9. Our study strengthens the hypothesis that leptin plays a role in the development of obesity-related delivery disorders.
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale (INSERM), U866, Lipides, Nutrition, Cancer, Dijon, France.
authors.forename: Maeva
authors.initials: M
authors.lastname: Wendremaire
authors.forename: Pascal
authors.initials: P
authors.lastname: Mourtialon
authors.forename: Françoise
authors.initials: F
authors.lastname: Goirand
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lirussi
authors.forename: Marina
authors.initials: M
authors.lastname: Barrichon
authors.forename: Tarik
authors.initials: T
authors.lastname: Hadi
authors.forename: Carmen
authors.initials: C
authors.lastname: Garrido
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Ray
authors.forename: Monique
authors.initials: M
authors.lastname: Dumas
authors.forename: Paul
authors.initials: P
authors.lastname: Sagot
authors.forename: Marc
authors.initials: M
authors.lastname: Bardou
mesh_terms: D000328:Adult; D001706:Biopsy; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005260:Female; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D020738:Leptin / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism / Q000473:pathology
chemical_list: D050958:HSP47 Heat-Shock Proteins; D020738:Leptin; D008070:Lipopolysaccharides; D003094:Collagen; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9