Sahin Ersoy Gulcin, Zhou Yuping, İnan Hamdi, Taner Cuneyt E, Cosar Emine, Taylor Hugh S
1 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.
2 Department of Obstetrics and Gynecology, Tepecik Education and Research Hospital, Izmir, Turkey.
Reprod Sci. 2017 Jul;24(7):989-995. doi: 10.1177/1933719117697129. Epub 2017 Mar 13.
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.
吸烟对生育能力及其他子宫内膜疾病的发病率有负面影响。为确定吸烟对子宫内膜生理功能的影响，我们在体外和体内评估了两种子宫内膜调节细胞因子及着床接受性标志物，即C-X-C基序趋化因子配体12（CXCL12）和成纤维细胞生长因子2（FGF2）。
用人子宫内膜基质细胞系（HESC）和原代人子宫内膜基质细胞分别用香烟烟雾提取物（CSE）或溶剂对照处理。20只雌性小鼠被随机分为两组，一组暴露于香烟烟雾（CS）8周，另一组为吸入室内空气的非吸烟（NS）组。对小鼠子宫组织进行CXCL12和FGF2表达的免疫组织化学分析。从非吸烟者和吸烟者中获取人子宫内膜样本。对所有细胞培养物和人样本进行实时逆转录-聚合酶链反应。
与对照组相比，暴露于CSE的HESC和原代细胞中CXCL12和FGFmRNA表达显著降低。在小鼠中，免疫组织化学分析显示，与对照组相比，CS组中CXCL12和FGF2蛋白表达均较低。同样，与非吸烟者相比，吸烟女性中CXCL12和FGF2表达均降低。
子宫内膜CXCL12和FGF2表达降低导致吸烟女性子宫内膜着床接受性受损。吸烟还与子宫内膜癌和子宫内膜异位症发病率降低有关；CXCL12和FGF2升高与这两种疾病均有关。此处描述的细胞因子表达变化可能解释吸烟对所有这些疾病的影响。烟草对正常子宫内膜有直接影响，进而影响子宫内膜健康和疾病。
