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Inter-individual variations and modulators of MDR1 transport activity in human placenta

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机构: [a]The Department of Clinical Pharmacy, The First Affiliated Hospital of Kunming Medical University, Kunming, China [b]Second Affiliated Hospital of Yunnan University of Chinese Medicine, China [c]The Department of Clinical pharmacy The First Affiliated Hospital of Kunming Medical University, No. 295, XiChang Road Kunming, China.
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关键词: ABCB1 MDR1 Placenta Transporter activity

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Introduction: ATP binding cassette (ABC) membrane transporter multidrug resistance 1 (MDR1) is one of the most important efflux transporters in the human placenta protecting the fetus from exposure to xenobiotic toxicity. Recent studies have focused on placental MDR1 expression, but few studies have analyzed placental MDR1 transport activity. The purpose of this study was to investigate placental MDR1 transport activity using a relatively large sample size of human placentas. Furthermore, the effect of ABCB1 gene polymorphisms were investigated along with physiological factors including maternal age, times of pregnancy, BMI, delivery mode or pregnancy complications on placental MDR1 transport activity. Methods: A total of 252 human placentas were obtained after delivery. MDR1 transport activity was detected by N-methyl quinidine uptake in placental microvillus membrane vesicles (MVMVs). Nine common single nucleotide polymorphisms (SNPs) in ABCB1 genes were determined by Snapshot. The association between ABCB1 gene polymorphisms, maternal age, times of pregnancy, BMI, delivery mode or pregnancy complications, and transporter activity was investigated. Results: Inter-individual variations of MDR1 transport activity were observed among 252 subjects. The per unit protein activity was ranged from 0.05 to 0.15/mg. Nine SNPs in ABCB1 gene didn't exhibit significant association with transporter activity of MDR1. Likewise, neither age, times of pregnancy, delivery mode nor pregnancy complications showed any significant effect of placental MDR1 transport activity. But placental MDR1 transport activity in obese pregnant women was lower than those in non-obese pregnant women. Conclusion: Inter-individual variations of MDR1 transport activity existed in human placentas. This may contribute to variations in drug exposure to the fetus affecting clinical outcomes. Maternal age, times of pregnancy, delivery mode nor pregnancy complications included in this study maybe not significantly impact placental MDR1 transport activity, but maternal obese could inhibit placental MDR1 activity. © 2020

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出版当年[2021]版:
大类 | 3 区 医学
小类 | 2 区 妇产科学 3 区 发育生物学 3 区 生殖生物学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 发育生物学 2 区 妇产科学 2 区 生殖生物学
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出版当年[2020]版:
Q2 REPRODUCTIVE BIOLOGY Q2 DEVELOPMENTAL BIOLOGY Q2 OBSTETRICS & GYNECOLOGY
最新[2023]版:
Q1 OBSTETRICS & GYNECOLOGY Q2 DEVELOPMENTAL BIOLOGY Q2 REPRODUCTIVE BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

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第一作者机构: [a]The Department of Clinical Pharmacy, The First Affiliated Hospital of Kunming Medical University, Kunming, China
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通讯机构: [c]The Department of Clinical pharmacy The First Affiliated Hospital of Kunming Medical University, No. 295, XiChang Road Kunming, China.
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