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Induction of size-dependent breakdown of blood-milk barrier in lactating mice by TiO2 nanoparticles.

Zhang C, Zhai S, Wu L, Bai Y, Jia J, Zhang Y, Zhang B, Yan B - PLoS ONE (2015)

Bottom Line: This accumulation of TiO2 NP likely causes a ROS-induced disruption of tight junction of the blood-milk barrier as indicated by the loss of tight junction proteins and the shedding of alveolar epithelial cells.An alarming finding is that the smaller TNPs (8 nm) are transferred from dams to pups through breastfeeding, likely through the disrupted blood-milk barrier.However, during the lactation period, the nutrient quality of milk from dams and the early developmental landmarks of the pups are not affected by above perturbations.

View Article: PubMed Central - PubMed

Affiliation: School of Chemistry and Chemical Engineering, Shandong University, Jinan, China.

ABSTRACT
This study aims to investigate the potential nanotoxic effects of TiO2 nanoparticles (TNPs) to dams and pups during lactation period. TiO2 nanoparticles are accumulated in mammary glands of lactating mice after i.v. administration. This accumulation of TiO2 NP likely causes a ROS-induced disruption of tight junction of the blood-milk barrier as indicated by the loss of tight junction proteins and the shedding of alveolar epithelial cells. Compared to larger TNPs (50 nm), smaller ones (8 nm) exhibit a higher accumulation in mammary glands and are more potent in causing perturbations to blood-milk barrier. An alarming finding is that the smaller TNPs (8 nm) are transferred from dams to pups through breastfeeding, likely through the disrupted blood-milk barrier. However, during the lactation period, the nutrient quality of milk from dams and the early developmental landmarks of the pups are not affected by above perturbations.

No MeSH data available.


Related in: MedlinePlus

Effects of TNPs on mammary gland tight junction proteins ZO-1 and occludin after four doses of TNPs exposure (2, 6, 8 mg/kg) to dams at LDs 2, 4, 6 and 8.(A) A plausible mechanistic schematic showing TNPs made cell shedding and loose the tight junction between the mammary gland epithelial cells through oxidative stress. (B) Western blot of ZO-1 and occludin in mammary glands. (C) Bar graphs show relative levels of tight junction proteins ZO-1 and occludin by normalizing PBS group to 1.0. The symbol * represents significant difference from the PBS group (P<0.05), (n = 3).
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pone.0122591.g005: Effects of TNPs on mammary gland tight junction proteins ZO-1 and occludin after four doses of TNPs exposure (2, 6, 8 mg/kg) to dams at LDs 2, 4, 6 and 8.(A) A plausible mechanistic schematic showing TNPs made cell shedding and loose the tight junction between the mammary gland epithelial cells through oxidative stress. (B) Western blot of ZO-1 and occludin in mammary glands. (C) Bar graphs show relative levels of tight junction proteins ZO-1 and occludin by normalizing PBS group to 1.0. The symbol * represents significant difference from the PBS group (P<0.05), (n = 3).

Mentions: Previous studies have shown that transcytosis of nanoparticles through endothelial cell layers is a rare event [49, 50]. The tight junction proteins ZO-1 and occludin are two key proteins that maintain the integrity of epithelial cell tight junctions in mammary glands [51]. Because TNPs induced local oxidative stress in mammary glands, we hypothesized that this might compromise the tight junctions of the blood-milk barrier by down-regulating the expression of integral proteins occludin and ZO-1 (Fig 5A). To test this hypothesis, we quantitatively analyzed the expression of occludin and ZO-1 in mammary gland tissues using Western blot and band intensity analysis with ImageJ software (Wayne Rasband, NIH, Bethesda, Maryland, USA). We observed a dose-dependent decrease of both proteins (Fig 5B and 5C). These results indicated that exposure of the dams to TNPs caused a reduced expression of key tight junction proteins ZO-1 and occludin and the shedding of epithelial cells in the mammary glands. We speculate that TNP-induced oxidative stress in mammary glands may be associated with cell shedding and the loss of tight junction proteins. However, whether there is casual link between cell shedding and tight junction disruption awaits further investigations. These perturbations significantly compromised the integrity of the blood-milk barrier. As a result, a possibility may exist that TNPs may leak into milk and reach the GI tracts of pups during milk feeding.


Induction of size-dependent breakdown of blood-milk barrier in lactating mice by TiO2 nanoparticles.

Zhang C, Zhai S, Wu L, Bai Y, Jia J, Zhang Y, Zhang B, Yan B - PLoS ONE (2015)

Effects of TNPs on mammary gland tight junction proteins ZO-1 and occludin after four doses of TNPs exposure (2, 6, 8 mg/kg) to dams at LDs 2, 4, 6 and 8.(A) A plausible mechanistic schematic showing TNPs made cell shedding and loose the tight junction between the mammary gland epithelial cells through oxidative stress. (B) Western blot of ZO-1 and occludin in mammary glands. (C) Bar graphs show relative levels of tight junction proteins ZO-1 and occludin by normalizing PBS group to 1.0. The symbol * represents significant difference from the PBS group (P<0.05), (n = 3).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4388820&req=5

pone.0122591.g005: Effects of TNPs on mammary gland tight junction proteins ZO-1 and occludin after four doses of TNPs exposure (2, 6, 8 mg/kg) to dams at LDs 2, 4, 6 and 8.(A) A plausible mechanistic schematic showing TNPs made cell shedding and loose the tight junction between the mammary gland epithelial cells through oxidative stress. (B) Western blot of ZO-1 and occludin in mammary glands. (C) Bar graphs show relative levels of tight junction proteins ZO-1 and occludin by normalizing PBS group to 1.0. The symbol * represents significant difference from the PBS group (P<0.05), (n = 3).
Mentions: Previous studies have shown that transcytosis of nanoparticles through endothelial cell layers is a rare event [49, 50]. The tight junction proteins ZO-1 and occludin are two key proteins that maintain the integrity of epithelial cell tight junctions in mammary glands [51]. Because TNPs induced local oxidative stress in mammary glands, we hypothesized that this might compromise the tight junctions of the blood-milk barrier by down-regulating the expression of integral proteins occludin and ZO-1 (Fig 5A). To test this hypothesis, we quantitatively analyzed the expression of occludin and ZO-1 in mammary gland tissues using Western blot and band intensity analysis with ImageJ software (Wayne Rasband, NIH, Bethesda, Maryland, USA). We observed a dose-dependent decrease of both proteins (Fig 5B and 5C). These results indicated that exposure of the dams to TNPs caused a reduced expression of key tight junction proteins ZO-1 and occludin and the shedding of epithelial cells in the mammary glands. We speculate that TNP-induced oxidative stress in mammary glands may be associated with cell shedding and the loss of tight junction proteins. However, whether there is casual link between cell shedding and tight junction disruption awaits further investigations. These perturbations significantly compromised the integrity of the blood-milk barrier. As a result, a possibility may exist that TNPs may leak into milk and reach the GI tracts of pups during milk feeding.

Bottom Line: This accumulation of TiO2 NP likely causes a ROS-induced disruption of tight junction of the blood-milk barrier as indicated by the loss of tight junction proteins and the shedding of alveolar epithelial cells.An alarming finding is that the smaller TNPs (8 nm) are transferred from dams to pups through breastfeeding, likely through the disrupted blood-milk barrier.However, during the lactation period, the nutrient quality of milk from dams and the early developmental landmarks of the pups are not affected by above perturbations.

View Article: PubMed Central - PubMed

Affiliation: School of Chemistry and Chemical Engineering, Shandong University, Jinan, China.

ABSTRACT
This study aims to investigate the potential nanotoxic effects of TiO2 nanoparticles (TNPs) to dams and pups during lactation period. TiO2 nanoparticles are accumulated in mammary glands of lactating mice after i.v. administration. This accumulation of TiO2 NP likely causes a ROS-induced disruption of tight junction of the blood-milk barrier as indicated by the loss of tight junction proteins and the shedding of alveolar epithelial cells. Compared to larger TNPs (50 nm), smaller ones (8 nm) exhibit a higher accumulation in mammary glands and are more potent in causing perturbations to blood-milk barrier. An alarming finding is that the smaller TNPs (8 nm) are transferred from dams to pups through breastfeeding, likely through the disrupted blood-milk barrier. However, during the lactation period, the nutrient quality of milk from dams and the early developmental landmarks of the pups are not affected by above perturbations.

No MeSH data available.


Related in: MedlinePlus