Prenatal tobacco use among Alaska Native (AN) women has decreased substantially over the past two decades. Previous research suggests that providing AN women with feedback regarding fetal exposure to tobacco may further promote cessation. Transporters in the placenta regulate fetal exposure to nutrients and xenobiotics, including compounds associated with tobacco use. We examined whether prenatal tobacco use impacts transporter expression in the placenta, and whether this is influenced by fetal sex, degree of tobacco exposure, or transporter genotype. At delivery, we obtained placental samples from AN research participants who smoked cigarettes, used commercial chew or iqmik (oral tobacco), or did not use tobacco during pregnancy. Transporter expression was evaluated using qRT-PCR and Western blotting and tested for correlations between transcript levels and urinary biomarkers of tobacco use. The impact of BCRP/ABCG2 and OATP2B1/SLCO2B1 genotypes on protein expression was also examined. Oral tobacco use was associated with decreased P-gp and increased MRP1, MRP3, LAT1, and PMAT mRNA expression. Transcript levels of multiple transporters significantly correlated with tobacco biomarkers in maternal and fetal urine. In women carrying male fetuses, both smoking and oral tobacco were associated with decreased P-gp. Oral tobacco was also associated with decreased LAT1 in women carrying female fetuses. BCRP and OATP2B1 genotypes did not appear to impact protein expression. In conclusion, prenatal tobacco use is associated with altered expression of multiple placental transporters which differs by fetal sex. As transcript levels of multiple transporters were significantly correlated with tobacco use biomarkers, eliminating prenatal tobacco use should alleviate these changes.

中文翻译：

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烟草使用对阿拉斯加土著妇女胎盘转运蛋白表达的影响

在过去二十年中，阿拉斯加原住民 (AN) 妇女的产前烟草使用量大幅减少。先前的研究表明，向 AN 女性提供有关胎儿接触烟草的反馈可能会进一步促进戒烟。胎盘中的转运蛋白调节胎儿接触营养物质和异生素，包括与烟草使用相关的化合物。我们检查了产前吸烟是否影响胎盘中的转运蛋白表达，以及这是否受胎儿性别、烟草暴露程度或转运蛋白基因型的影响。在分娩时，我们从 AN 研究参与者那里获得了胎盘样本，这些参与者抽过香烟，使用过商业咀嚼物或 iqmik（口服烟草），或者在怀孕期间没有使用过烟草。使用 qRT-PCR 和蛋白质印迹评估转运蛋白表达，并测试转录物水平与烟草使用的尿液生物标志物之间的相关性。的影响还检查了BCRP/ABCG2和OATP2B1/SLCO2B1基因型对蛋白质表达的影响。口服烟草使用与P-gp降低和MRP1、MRP3、LAT1和PMAT mRNA 表达增加有关。多种转运蛋白的转录水平与母体和胎儿尿液中的烟草生物标志物显着相关。在怀有男性胎儿的女性中，吸烟和口服烟草都与 P-gp 降低有关。口服烟草也与怀有女性胎儿的女性的 LAT1 降低有关。BCRP和OATP2B1基因型似乎不影响蛋白质表达。总之，产前吸烟与多种胎盘转运蛋白的表达改变有关，这种改变因胎儿性别而异。由于多种转运蛋白的转录水平与烟草使用生物标志物显着相关，因此消除产前烟草使用应该可以减轻这些变化。