The Effect of Tobacco Use on the Expression of Placental Transporters in Alaska Native Women

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.

Diversity, Equity, and Inclusion: Translating Clinical Pharmacology for All

“…Research in pharmacogenomics should include diverse populations as genetic polymorphisms that influence drug response may have different allele frequencies in different populations or even be population specific. Inclusive translational and pharmacogenomics research that nurtures participation of historically excluded, admixed, and minority populations across all geographies is imperative 3–7 . In a Perspective, Sitabule et al 8 .…”

“…Inclusive translational and pharmacogenomics research that nurtures participation of historically excluded, admixed, and minority populations across all geographies is imperative. [3][4][5][6][7] In a Perspective, Sitabule et al 8 posit that African populations have more genetic variation than other geographic groups, emphasizing the critical importance of promoting pharmacogenomics research in Africa in the context of the growing burden of both infectious and noninfectious diseases impacting the continent and globe. A major barrier to inclusion in pharmacogenomic research has been a lack of trust particularly from historically excluded populations.…”

Occurrence of Oral Premalignant Lesions Among Tobacco Users in a Tribal Population: A Systematic Review and Meta-Analysis

“…Among these marginalised communities are tribal populations, which are generally known for their nomadic lifestyle and practices, including detrimental tobacco-related habits [25]. Despite their unique cultural and health characteristics, there is a paucity of scientific literature documenting the prevalence of oral lesions within this distinct tribal population [26].…”

“…Numerous studies have been conducted to explore the prevalence of oral precancerous lesions in different populations, shedding light on the distribution and gender-specific patterns of these lesions. One paper [9,26,27] reported a higher prevalence of OSMF and leukoplakia in males. Similarly, another article [28] observed a significantly higher prevalence of precancerous lesions among males (5.5%) compared to females in the general population of the Telangana region, India.…”

In silico modeling for ex vivo placenta perfusion of nicotine

“…Therefore, it seems that the placenta plays a little role as a barrier for nicotine from the maternal to fetal side (m → f) (Pastrakuljic et al, 1998). However, the extraction of nicotine from the fetal to the maternal side (f → m) is more complicated, as the process is modulated by organic cation transporters (OCTs) (Lin et al, 2022), and possibly other transporters, e.g., P-gp as well (McColl et al, 2023). In human beings, OCT3 is the only OCT isoform expressed at placental basal membrane vesicles (Sata et al, 2005).…”