Abstract

Some chemicals are ligands to efflux transporters which may result in high concentrations in milk. Limited knowledge is available on the influence of maternal exposure to chemicals on the expression and function of transporters in the lactating mammary gland. We determined gene expression of ABC and SLC transporters in murine mammary tissue of different gestation and lactation stages, in murine mammary cells (HC11) featuring resting and secreting phenotypes and in bovine mammary tissue and cells (BME-UV). Effects on transporter expression and function of the imidazole fungicide prochloraz, previously reported to influence BCRP in mammary cells, was investigated on transporter expression and function in the two cell lines. Transporters studied were BCRP, MDR1, MRP1, OATP1A5/OATP1A2, OCTN1 and OCT1. Gene expressions of BCRP and OCT1 in murine mammary glands were increased during gestation and lactation, whereas MDR1, MRP1, OATP1A5 and OCTN1 were decreased, compared to expressions in virgins. All transporters measured in mammary glands of mice were detected in bovine mammary tissue and in HC11 cells, while only MDR1 and MRP1 were detected in BME-UV cells. Prochloraz treatment induced MDR1 gene and protein expression in both differentiated HC11 and BME-UV cells and increased protein function in HC11 cells, resulting in decreased accumulation of the MDR1 substrate digoxin. In conclusion, our results demonstrate that murine (HC11) and bovine (BME-UV) mammary epithelial cells can be applied to characterize expression and function of transporters as well as effects of contaminants on the mammary transporters. An altered expression, induced by a drug or toxic chemical, on any of the transporters expressed in the mammary epithelial cells during lactation may modulate the well-balanced composition of nutrients and/or secretion of contaminants in milk with potential adverse effects on breast-fed infants and dairy consumers.

Published in

PLoS ONE
2016, Volume: 11, number: 3, article number: e0151904
Publisher: PUBLIC LIBRARY SCIENCE

SLU Authors

• Yagdiran, Yagmur

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

• Oskarsson, Agneta

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

• Tallkvist, Jonas

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

Associated SLU-program

AMR: Fungus


Sustainable Development Goals

Ensure healthy lives and promote well-being for all at all ages


UKÄ Subject classification

Biochemistry and Molecular Biology
Pharmacology and Toxicology


Publication identifier

DOI: https://doi.org/10.1371/journal.pone.0151904

Permanent link to this page (URI)

https://res.slu.se/id/publ/79368