Effect Of Visfatin On Contractility Related Gene Expression In A Human Myometrial Cell Line

Obesity is risk factor for dysfunctional labor and cesarean delivery. The etiology remains unclear. Visfatin, a novel adipokine, is highly expressed in visceral adipose tissue. Plasma visfatin levels increase with obesity and has been reported to have cumulative inhibitory effect on spontaneous and oxytocin induced myometrial contractility (Mumtaz et al, 2015). However, molecular mechanism of contractility inhibition remains unclear. The objective of this study is to investigate the effects of visfatin on the expression of genes associated with uterine contractility using a myometrial cell line treated ±oxytocin. Immortalized human myometrial (PHM1-41) cells were exposed to either vehicle or visfatin(50nM) for 24hrs. Cytotoxicity assays confirmed this dose was non-cytotoxic. The expression of mRNAs encoding oxytocin (OXT), oxytocin receptor (OXTR) and gap junction-related Debrin-1 (DBN1) were analyzed by real time qRT-PCR. In addition, either vehicle or visfatin(50nM) pretreated cells were then treated ±oxytocin for 2hrs and gene expression was assessed. Vehicle vs. visfatin data were analyzed using unpaired t tests with Welch’s correction and combination treatment data were analyzed using non-parametric Kruskal-Wallis test, followed by Dunn’s multiple comparisons. P<0.05 was considered significant. Treatment of PHM1-41 myometrial cells with visfatin alone significantly induced oxytocin induced genes (OXT mRNA and OXTR mRNA) expression by human myometrial cells (p=0.02) but did not change DBN1 mRNA expression (Figure 1). When combined with oxytocin, visfatin showed no difference in expression of contractility related genes (OXT, OXTR and DBN1). Our results suggest that visfatin alone significantly induces oxytocin-induced contractility genes (OXT mRNA and OXTR mRNA expression). However, this effect was not seen in combination treatment with oxytocin.