학술논문

The Effect of Tobacco Use on the Expression of Placental Transporters in Alaska Native Women
Document Type
article
Source
Clinical Pharmacology & Therapeutics. 113(3)
Subject
Reproductive Medicine
Biomedical and Clinical Sciences
Infant Mortality
Perinatal Period - Conditions Originating in Perinatal Period
Substance Misuse
Conditions Affecting the Embryonic and Fetal Periods
Tobacco
Pediatric
Tobacco Smoke and Health
Clinical Research
Genetics
Prevention
Cancer
Reproductive health and childbirth
Good Health and Well Being
Female
Pregnancy
Male
Humans
Placenta
ATP Binding Cassette Transporter
Subfamily G
Member 2
Neoplasm Proteins
Membrane Transport Proteins
Tobacco Use
Biomarkers
Pharmacology and Pharmaceutical Sciences
Pharmacology & Pharmacy
Pharmacology and pharmaceutical sciences
Language
Abstract
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.