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Vol 85, No 6 (2014)
ARTICLES
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Immunolocalization of ABC drug transporters in human placenta from normal and gestational diabetic pregnancies

Danuta Kozłowska-Rup, Piotr Czekaj, Danuta Plewka, Jerzy Sikora
DOI: 10.17772/gp/1745
·
Ginekol Pol 2014;85(6).

open access

Vol 85, No 6 (2014)
ARTICLES

Abstract

Objectives: ABC transporters, P-gp, MDR3, BCRP and MRP1, can bind both endo- and exogenous ligands. The latter include immunosuppressive, anticancer, sedative, anticonvulsant, antiparasitic and cardiovascular drugs, as well as HIV protease inhibitors and antibiotics. Protein transporters are also involved in tissue distribution of orally administered medicines in combination therapy for gestational diabetes mellitus (GDM) and could be used during GDM treatment. The distribution depends on transporter specificity, its expression and subcellular localization. The aim: The aim of the study was to compare P-gp, MDR3, BCRP and MRP1 localization in placental tissues from normal and GDM diabetic pregnancies. Material and methods: Tissue samples were taken from 10 normal and 10 GDM placentas. Immunohistochemical reactions were performed with the use of adequate monoclonal antibodies. Avidin-biotin-peroxidase complex method was used for the visualization of antigen-antibody complexes. Results: P-gp, MDR3 and BCRP were found in all parts of normal human placenta i.e. the amniotic epithelium, cytotrophoblast, syncytiotrophoblast and decidual cells. P-gp and BCRP, but not MDR3 and MRP1, were also localized on the endothelial cells of fetal blood vessels in the chorionic plate, as well as stem and tertiary villi. MRP1 expression was observed in the cytotrophoblast and the syncytiotrophoblast. Its expression was very low or undetectable in the amniotic epithelium and the majority of decidual cells. Immunohistochemical reactions within the syncytiotrophoblast showed apical (P-gp, BCRP), apical and basal (MRP1) or diffuse (MDR3) distribution. The main changes observed in GDM placentas included weaker MRP1 and MDR3 positive reactions in the syncytiotrophoblast, slightly lower expression of P-gp in the decidual and amniotic epithelial cells, and MDR3 in the amniotic epithelium. Conclusions: Our results indicate that GDM-related changes in the environment of placental cells do not substantially influence tissue and subcellular location of ABC transporters. Nevertheless, the expression of P-gp, MDR3 and MRP1 may be lower in comparison to normal placentas. Basal syncytiotrophoblast transporters, MRP1 and MDR3, seem to be more sensitive to the influence of GDM than apical proteins, what may result in altered biodisposition of endogenous substrates and drugs.

Abstract

Objectives: ABC transporters, P-gp, MDR3, BCRP and MRP1, can bind both endo- and exogenous ligands. The latter include immunosuppressive, anticancer, sedative, anticonvulsant, antiparasitic and cardiovascular drugs, as well as HIV protease inhibitors and antibiotics. Protein transporters are also involved in tissue distribution of orally administered medicines in combination therapy for gestational diabetes mellitus (GDM) and could be used during GDM treatment. The distribution depends on transporter specificity, its expression and subcellular localization. The aim: The aim of the study was to compare P-gp, MDR3, BCRP and MRP1 localization in placental tissues from normal and GDM diabetic pregnancies. Material and methods: Tissue samples were taken from 10 normal and 10 GDM placentas. Immunohistochemical reactions were performed with the use of adequate monoclonal antibodies. Avidin-biotin-peroxidase complex method was used for the visualization of antigen-antibody complexes. Results: P-gp, MDR3 and BCRP were found in all parts of normal human placenta i.e. the amniotic epithelium, cytotrophoblast, syncytiotrophoblast and decidual cells. P-gp and BCRP, but not MDR3 and MRP1, were also localized on the endothelial cells of fetal blood vessels in the chorionic plate, as well as stem and tertiary villi. MRP1 expression was observed in the cytotrophoblast and the syncytiotrophoblast. Its expression was very low or undetectable in the amniotic epithelium and the majority of decidual cells. Immunohistochemical reactions within the syncytiotrophoblast showed apical (P-gp, BCRP), apical and basal (MRP1) or diffuse (MDR3) distribution. The main changes observed in GDM placentas included weaker MRP1 and MDR3 positive reactions in the syncytiotrophoblast, slightly lower expression of P-gp in the decidual and amniotic epithelial cells, and MDR3 in the amniotic epithelium. Conclusions: Our results indicate that GDM-related changes in the environment of placental cells do not substantially influence tissue and subcellular location of ABC transporters. Nevertheless, the expression of P-gp, MDR3 and MRP1 may be lower in comparison to normal placentas. Basal syncytiotrophoblast transporters, MRP1 and MDR3, seem to be more sensitive to the influence of GDM than apical proteins, what may result in altered biodisposition of endogenous substrates and drugs.
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Keywords

ABC drug transporters, breast cancer resistance protein BCRP, P-glycoprotein, multidrug resistance protein MDR3, multidrug resistance-associated protein MRP1, human placenta, Gestational diabetes mellitus

About this article
Title

Immunolocalization of ABC drug transporters in human placenta from normal and gestational diabetic pregnancies

Journal

Ginekologia Polska

Issue

Vol 85, No 6 (2014)

DOI

10.17772/gp/1745

Bibliographic record

Ginekol Pol 2014;85(6).

Keywords

ABC drug transporters
breast cancer resistance protein BCRP
P-glycoprotein
multidrug resistance protein MDR3
multidrug resistance-associated protein MRP1
human placenta
Gestational diabetes mellitus

Authors

Danuta Kozłowska-Rup
Piotr Czekaj
Danuta Plewka
Jerzy Sikora

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