Lactation during cholestasis: Role of ABC proteins in bile acid traffic across the mammary gland

Abstract Transporters involved in bile acid (BA) handling by the mammary gland are poorly understood. Here we have investigated the role of ABC proteins in blood-milk BA traffic and its sensitivity to maternal cholestasis. BA concentrations in rat and mouse serum were higher than in milk. BA profile...

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Autores principales: Alba M. G. Blazquez, Rocio I. R. Macias, Candela Cives-Losada, Alberto de la Iglesia, Jose J. G. Marin, Maria J. Monte
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/7420089d0fcb4fc2bbcafa376e74fce2
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spelling oai:doaj.org-article:7420089d0fcb4fc2bbcafa376e74fce22021-12-02T15:05:49ZLactation during cholestasis: Role of ABC proteins in bile acid traffic across the mammary gland10.1038/s41598-017-06315-82045-2322https://doaj.org/article/7420089d0fcb4fc2bbcafa376e74fce22017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06315-8https://doaj.org/toc/2045-2322Abstract Transporters involved in bile acid (BA) handling by the mammary gland are poorly understood. Here we have investigated the role of ABC proteins in blood-milk BA traffic and its sensitivity to maternal cholestasis. BA concentrations in rat and mouse serum were higher than in milk. BA profiles in both fluids were also different. In mammary gland, mRNA levels of ABC pumps transporting BAs were high for Bcrp, less abundant for Mrp1, Mrp3 and Mrp4 and negligible for Bsep and Mrp2. Milk BA concentrations were lower in Abcg2 −/− than in wild-type mice. Taurocholate administration (5 µmol, i.p.) increased 20-fold BA concentrations in serum, but only moderately in milk, even in Abcg2 −/− mice. Bile duct ligation (BDL) in pregnant rats markedly increased serum BA concentrations, which was not proportionally reflected in milk. In rat mammary tissue, Mrp4 was up-regulated by BDL. Serum BA levels were 2-fold higher in 10-day-old neonates of the BDL group, whereas their body weight was lower. The exchange of breastfeeding mothers immediately after birth reverted the situation without changes in endogenous BA synthesis. In conclusion, Bcrp is involved in BA secretion into milk, whereas Mrp4 participates in a blood-milk barrier that protects neonates from maternal hypercholanemia during breastfeeding.Alba M. G. BlazquezRocio I. R. MaciasCandela Cives-LosadaAlberto de la IglesiaJose J. G. MarinMaria J. MonteNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Alba M. G. Blazquez
Rocio I. R. Macias
Candela Cives-Losada
Alberto de la Iglesia
Jose J. G. Marin
Maria J. Monte
Lactation during cholestasis: Role of ABC proteins in bile acid traffic across the mammary gland
description Abstract Transporters involved in bile acid (BA) handling by the mammary gland are poorly understood. Here we have investigated the role of ABC proteins in blood-milk BA traffic and its sensitivity to maternal cholestasis. BA concentrations in rat and mouse serum were higher than in milk. BA profiles in both fluids were also different. In mammary gland, mRNA levels of ABC pumps transporting BAs were high for Bcrp, less abundant for Mrp1, Mrp3 and Mrp4 and negligible for Bsep and Mrp2. Milk BA concentrations were lower in Abcg2 −/− than in wild-type mice. Taurocholate administration (5 µmol, i.p.) increased 20-fold BA concentrations in serum, but only moderately in milk, even in Abcg2 −/− mice. Bile duct ligation (BDL) in pregnant rats markedly increased serum BA concentrations, which was not proportionally reflected in milk. In rat mammary tissue, Mrp4 was up-regulated by BDL. Serum BA levels were 2-fold higher in 10-day-old neonates of the BDL group, whereas their body weight was lower. The exchange of breastfeeding mothers immediately after birth reverted the situation without changes in endogenous BA synthesis. In conclusion, Bcrp is involved in BA secretion into milk, whereas Mrp4 participates in a blood-milk barrier that protects neonates from maternal hypercholanemia during breastfeeding.
format article
author Alba M. G. Blazquez
Rocio I. R. Macias
Candela Cives-Losada
Alberto de la Iglesia
Jose J. G. Marin
Maria J. Monte
author_facet Alba M. G. Blazquez
Rocio I. R. Macias
Candela Cives-Losada
Alberto de la Iglesia
Jose J. G. Marin
Maria J. Monte
author_sort Alba M. G. Blazquez
title Lactation during cholestasis: Role of ABC proteins in bile acid traffic across the mammary gland
title_short Lactation during cholestasis: Role of ABC proteins in bile acid traffic across the mammary gland
title_full Lactation during cholestasis: Role of ABC proteins in bile acid traffic across the mammary gland
title_fullStr Lactation during cholestasis: Role of ABC proteins in bile acid traffic across the mammary gland
title_full_unstemmed Lactation during cholestasis: Role of ABC proteins in bile acid traffic across the mammary gland
title_sort lactation during cholestasis: role of abc proteins in bile acid traffic across the mammary gland
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/7420089d0fcb4fc2bbcafa376e74fce2
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