(338) Leptin Alters Myometrial Contractility-Related Gene Expression in a Human Myometrial Cell Line

Objective: Obesity is linked with poor labor progression and increased cesarean deliveries. Dysfunctional labor in the setting of obesity is hypothesized to result from reduced myometrial contractility. Leptin levels rise with obesity and are reported to inhibit spontaneous and oxytocin-induced myometrial contractility (Moynihan et al, 2006). However, the underlying biologic mechanisms by which leptin produces this effect is unknown. We investigated the effects of leptin on the expression of genes associated with uterine contractility in a myometrial cell line treated ±oxytocin.

Study Design: Immortalized human myometrial (PHM1-41) cells were treated with vehicle or leptin (1μM) for 24 hours. Cytotoxicity assays confirmed non-cytotoxicity of this dose. The expression of mRNAs encoding oxytocin (OXT), oxytocin receptor (OXTR) and gap junction-related Debrin-1 (DBN1) were analyzed by real time qRT-PCR. Cells pretreated with either vehicle or leptin (1μM) were subsequently exposed to oxytocin for 2 hours, and gene expression was re-assessed. Vehicle vs. leptin 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.

Results: Leptin treatment alone did not alter OXT mRNA or OXTR mRNA expression but significantly increased DBN1 mRNA expression (p=0.04). Oxytocin treatment increased OXT, OXTR and DBN1 mRNA expression compared to vehicle. Leptin significantly inhibited oxytocin-induced OXT mRNA expression (p< 0.01) and showed a non-significant trend towards reducing oxytocin-induced OXTR and DBN1 mRNA expression when compared to vehicle+oxytocin treated cells (Figure 1).

Conclusion: Leptin alone did not affect OXT or OXTR mRNA expression in human myometrial cells but suppressed oxytocin-induced contractility-related gene expression. These novel findings suggest leptin’s role in modulating myometrial expression of contractility-related genes, offering insights into possible pathways contributing towards parturition dysfunction in obese individuals.