Cigarette Smoking Affects Uterine Receptivity Markers.

Abstract

Smoking negatively affects fertility and the rate of other endometrial diseases. To determine the effect of smoking on endometrial physiology, we evaluated 2 endometrial regulatory cytokines and receptivity markers, C-X-C motif chemokine ligand 12 (CXCL12) and fibroblast growth factor 2 (FGF2), both in vitro and in vivo. The human endometrial stromal cell line (HESC) and primary human endometrial stromal cells were treated with cigarette smoking extract (CSE) or with vehicle control. Twenty female mice were randomly assigned to either cigarette smoke (CS) exposure for 8 weeks or to a nonsmoke (NS) group that received room air. Immunohistochemical analysis of CXCL12 and FGF2 expression was performed in mouse uterine tissue. Human endometrial samples were obtained from both nonsmokers and smokers. Real-time reverse transcription-polymerase chain reaction was performed for all cell cultures and human samples. Compared to controls, CXCL12 and FGF2 mRNA expression were significantly decreased in CSE-exposed HESC and primary cells. In mice, immunohistochemical analysis showed that both CXCL12 and FGF2 protein expression was lower in the CS group compared to controls. Similarly, both CXCL12 and FGF2 expression were decreased in women who smoke compared to nonsmokers. Decreased endometrial CXCL12 and FGF2 expression contribute to the impaired endometrial receptivity in women who smoke. Smoking is also associated with decreased rates of endometrial cancer and endometriosis; increased CXCL12 and FGF2 are implicated in both conditions. The changes in the expression of cytokines described here may explain the impact of smoking on all of these diseases. Tobacco has direct effects on normal endometrium that impacts endometrial health and disease.