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.
Highlights
Milk and dairy products are valuable foods for humans constituting an important nutrient source [1] but may contain hazardous compounds [2,3,4]
Messenger RNA expressions of CSN2, BCRP, MDR1, MRP1, OATP1A5, OCTN1 and OCT1 in mammary gland tissues were measured in virgins and at different stages of gestation and lactation from mice
OCTN1 gene expression had a similar profile as MDR1 and MRP1 (Fig 1F)
Summary
Milk and dairy products are valuable foods for humans constituting an important nutrient source [1] but may contain hazardous compounds [2,3,4]. Chemicals are secreted from blood to milk either via passive diffusion or active transport. Transporters are transmembrane proteins involved in cellular in- and efflux of essential and non-essential chemicals. Because these transporters are highly expressed in epithelia of tissues they serve an important role in absorption, tissue distribution and excretion of drugs and other chemicals [8]. A vast knowledge has been gained during the last decades concerning transport protein function, localization and expression in many tissues of the body, there is limited data on transporters in the mammary gland and their role for secretion of contaminants into milk [7,8,9,10,11,12]. Very little attention has been paid to the influence of maternal exposure to chemicals on the expression and function of transporters in the lactating mammary gland
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