Cigarette smoke inhibits endometrial epithelial cell proliferation through a nitric oxide–mediated pathway

ObjectiveTo determine the direct effects of cigarette smoke (CS) on human endometrial surface epithelial cell line proliferation.DesignIn vitro study using HES cells and primary human endometrial cells.SettingUniversity-based academic center.Patient(s)Premenopausal women in the proliferative phase of the cycle.Intervention(s)The HES cells and primary human endometrial cells were exposed to cigarette smoke–saturated solution.Main Outcome Measure(s)Cell proliferation and expression of different isoforms of nitric oxide synthase.Result(s)Cigarette smoke inhibited HES cell proliferation in a dose- and time-dependant manner. The inhibitory effect of CS was blocked by hemoglobin and enhanced by L-arginine (L-Arg). Cigarette smoking and nicotine stimulated the expression of endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) whereas benzo[a]pyrene (BP) only stimulated the expression of eNOS in HES cells. Cigarette smoke stimulated the expression of eNOS/iNOS in primary human endometrial cells, comprised of epithelial and stromal cells. The effect of CS on eNOS/iNOS expression in HES cells was blocked by ascorbic acid but not by glutathione.Conclusion(s)Cigarette smoke inhibits endometrial cell proliferation through a nitric oxide–mediated pathway.