Effects of Leptin on Lipopolysaccharide-Induced Remodeling in an In Vitro Model of Human Myometrial Inflammation1

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.

Shedding of syndecan-4 promotes immune cell recruitment and mitigates cardiac dysfunction after lipopolysaccharide challenge in mice

“…Degradation of collagens has been observed in several cells and tissues after LPS challenge [42,43], and our findings of reduced cardiac fibroblast activation and collagen production after LPS are in line with these observations. Interestingly, these effects could be mediated by shed syndecan-4 ectodomains.…”

Inhibitory effect of visfatin and leptin on human and rat myometrial contractility

“…If such a relationship is present in myometrium then it could contribute to the decreased contractility associated with hypoxia and pH [52] change. Visfatin/NAMPT is also produced in greater amounts during stretch, leading to the suggestion that this is a mechanism of increasing metabolite supply for cytoskeletal rearrangement and then for the mechanical work of labour [53]. This pathway was also shown to be important in visfatin's relaxant effects in rat and human mesenteric microvessels [54].…”

Association between Obesity and Cervical Microflora Dominated by Lactobacillus iners in Korean Women

“…Obese women have been shown to have different physiological characteristics that may lead to dysbiosis of the genital tract, including high plasma estrogen levels, systemic inflammation, and low immune function (10,11). Furthermore, several previous studies showed that prepregnancy body mass index (BMI) and plasma leptin levels may influence the outcomes of pregnancies, such as preterm delivery, low-birth-weight infants, macrosomia, and delivery disorders (12,13). These obstetric and neonatal disorders were also associated with Lactobacillus inersdominant microbiota in early pregnancy and the presence of bacteria related to bacterial vaginosis, as detected by vaginal smears (8,(14)(15)(16).…”