The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Expression of the Multidrug Resistance P-Glycoprotein, (ABCB1 glycoprotein) in the Human Placenta Decreases with Advancing Gestation
Abstract
The multidrug resistance p-glycoprotein (P-gp), encoded by the ABCB1 gene, is a plasma membrane protein that actively extrudes a wide variety of substances from cells. Preliminary studies in mice have shown that the ABCB1/P-gp can protect the fetus from a number of toxic substances. ABCB1/P-gp is expressed in the human placenta and is potentially capable of protecting the fetus from a large number of drugs and toxins, including herbicides and pesticides. The protein can also extrude various steroids including certain glucocorticoids and may therefore play an important role in regulating fetal access of glucocorticoids. The aim of the present study was to examine the expression profile and cellular localization of ABCB1/P-gp in human placenta throughout gestation. We hypothesized that there would be gestational age-related changes in the expression of the protein. ABCB1/P-gp mRNA was measured by Real-Time PCR using specific probes in tissues obtained from 6 weeks gestation to term. ABCB1/P-gp mRNA levels in placental tissue obtained at 6-10 weeks (n=5) and 24-35 weeks (n=5) were significantly higher than in tissues obtained at term (38-41 weeks gestation) by elective C-section (n=6) or following labor (n=6). The profile of ABCB1/P-gp protein levels, quantified using Western analysis, demonstrated a similar decrease with advancing gestation. At all gestational ages ABCB1/P-gp was localized by immunohistochemistry to the syncytiotrophoblast. In term tissues, it appeared to be localized to some areas of the villi and not others. Together, these data indicate that with advancing gestation there is a decrease in the level of ABCB1/P-gp in the human placenta indicating that the fetus may be more susceptible to toxic insults in the latter part of gestation. Further, the reduction in ABCB1/P-gp expression may contribute to the increased transfer of maternal cortisol to the fetus that is known to occur in late gestation.
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“The mRNA and protein levels of P-glycoprotein reduce across gestation, suggesting the fetus may be more exposed to toxic insults later in pregnancy (519).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [519]
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Endocrine and Paracrine Regulation of Birth at Term and Preterm*
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Self-citationP-Glycoprotein, a gatekeeper in the blood–brain barrier
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Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone.
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Cytokines, Prostaglandins and Parturition—A Review
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Endocrine and Paracrine Regulation of Birth at Term and Preterm
Challis, J. R. G. (2000) · Endocrine Reviews · doi:10.1210/er.21.5.514 · Cited by 609
Placental 11β‐hydroxysteroid dehydrogenase: a key regulator of fetal glucocorticoid exposure
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Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation
Klaassen, C. D., & Aleksunes, L. M. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002014 · Cited by 818
Placental Origins of Chronic Disease
Burton, G. J., Fowden, A. L., & Thornburg, K. L. (2016) · Physiological Reviews · doi:10.1152/physrev.00029.2015 · Cited by 717
Fetal programming of hypothalamo‐pituitary‐adrenal function: prenatal stress and glucocorticoids
Kapoor, A., Dunn, E., Kostaki, A., Andrews, M. H., & Matthews, S. G. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.105254 · Cited by 598
Self-citationGlucocorticoids and fetal programming part 2: mechanisms
Moisiadis, V. G., & Matthews, S. G. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.74 · Cited by 448
Self-citationPharmacokinetics of drugs in pregnancy
Feghali, M. N., Venkataramanan, R., & Caritis, S. N. (2015) · Seminars in Perinatology · doi:10.1053/j.semperi.2015.08.003 · Cited by 377
Metadata
- Authors
- Sun, M., Kingdom, J., Baczyk, D., Lye, S. J., Matthews, S. G., & Gibb, W.
- Affiliations
- University of Ottawa (CA)
- Mount Sinai Hospital (CA)
- Corresponding author
- Gibb, W.
- Venue
- Placenta
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 27
- Issue
- 6-7
- Pages
- 602-609
- ISSN
- 0143-4004 (ISSN-L)
- OpenAlex
- W2021031411
- Cited by
- 223
- References
- 38
- Citations by year
- 2026: 4 · 2024: 3 · 2023: 9 · 2022: 16 · 2021: 14 · 2020: 13 · 2019: 11 · 2018: 16 · 2017: 10 · 2016: 8 · 2015: 13 · 2014: 12 · 2013: 20 · 2012: 17
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Placenta (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Keywords
- P-glycoprotein, multidrug resistance protein, human placenta, gestational age, syncytiotrophoblast
- MeSH terms
- Adult, Female, Gestational Age, Humans, Maternal-Fetal Exchange, Placenta, Pregnancy, RNA, Messenger, Blotting, Western, Drug Resistance, Multiple, Gene Expression Regulation, Developmental, Reverse Transcriptase Polymerase Chain Reaction, ATP Binding Cassette Transporter, Subfamily B, Member 1
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