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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

Shedding of mammary alveolar epithelial cells induced by TNPs.A. Schematic anatomical diagrams of lactating mammary glands during lactation period and cartoon indicates that ROS induced cell shedding. B. Representative histological micrographs of the mammary glands 10 days after treatment with (i) PBS; (ii) TNP-8 at a dose of 2 mg/kg; (iii) TNP-8 at a dose of 6 mg/kg; (iv) TNP-8 at a dose of 8 mg/kg. Cell shedding and barrier loosening are noted; (v) Severe cell shedding into alveolar lumen is evident at a dose of 8 mg/kg; (vi) An enlarged view of cell shedding. C. Representative histological micrographs of the mammary glands 10 days after treatment with (i) TNP-50 at a dose of 2 mg/kg; (ii) TNP-50 at a dose of 6 mg/kg; (iii) TNP-50 at a dose of 8 mg/kg; (iv) Cell shedding into alveolar lumen is observed at a dose of 8 mg/kg. D. Quantification of numbers of mammary alveolar epithelial cells shed into the alveolar lumen. There were 7 mice in each experimental group and around 100 alveoli images were examined for each mouse. Scale bar: 40 μm; Narrow arrows indicate gap; Thick arrows indicate cell shedding.
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pone.0122591.g004: Shedding of mammary alveolar epithelial cells induced by TNPs.A. Schematic anatomical diagrams of lactating mammary glands during lactation period and cartoon indicates that ROS induced cell shedding. B. Representative histological micrographs of the mammary glands 10 days after treatment with (i) PBS; (ii) TNP-8 at a dose of 2 mg/kg; (iii) TNP-8 at a dose of 6 mg/kg; (iv) TNP-8 at a dose of 8 mg/kg. Cell shedding and barrier loosening are noted; (v) Severe cell shedding into alveolar lumen is evident at a dose of 8 mg/kg; (vi) An enlarged view of cell shedding. C. Representative histological micrographs of the mammary glands 10 days after treatment with (i) TNP-50 at a dose of 2 mg/kg; (ii) TNP-50 at a dose of 6 mg/kg; (iii) TNP-50 at a dose of 8 mg/kg; (iv) Cell shedding into alveolar lumen is observed at a dose of 8 mg/kg. D. Quantification of numbers of mammary alveolar epithelial cells shed into the alveolar lumen. There were 7 mice in each experimental group and around 100 alveoli images were examined for each mouse. Scale bar: 40 μm; Narrow arrows indicate gap; Thick arrows indicate cell shedding.

Mentions: Mammary alveolar epithelial cells are polarized secretory cells (Fig 4A). These cells synthesize milk proteins and secrete milk. There are tight junctions between the basal (blood) and apical (milk) sides of alveolar epithelial cells. The vital function of this barrier is to prohibit the direct paracellular exchange of substances between vascular and milk compartments during the lactation period. Because peak lactation in rodents occurs on LD 10, we first preformed histological examination of the integrity of mammary glands at LD 10 (Fig 4B–4D). The mammary glands of the lactating dams after PBS treatment contained intact alveolar epithelial cells. There was no noticeable cell shedding into the alveolar lumen (Fig 4Bi). After treatment with TNP-8 or TNP-50 at 2 mg/kg, the mammary glands showed no pathological alterations compared to the PBS group (Fig 4Bii for TNP-8 and Fig 4Ci for TNP-50). As the exposure dose increased, more shedding of epithelial cells into the alveolar lumen was observed (Fig 4Biii for TNP-8 and Fig 4Cii for TNP-50). Cell shedding became more severe when dams were exposed to a higher dose of TNP (Fig 4Biv and v for TNP-8 and Fig 4Ciii and iv for TNP-50). At the highest dose used (8 mg/kg), hyperplasia and stress-induced adipocytes were observed only for TNP-8 treatment (S3A and S3B Fig). The loss of mammary gland epithelial cells may produce defects or gaps in the tight junction of blood-milk barrier. By examining seven mice per exposure group and approximately 100 histological images for each mouse, we quantitatively determined the number of shed cells after each exposure. Our data showed that the smaller TNPs caused more cell shedding than the larger TNPs and cell shedding induced by both TNPs was dose-dependent (Fig 4D).


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)

Shedding of mammary alveolar epithelial cells induced by TNPs.A. Schematic anatomical diagrams of lactating mammary glands during lactation period and cartoon indicates that ROS induced cell shedding. B. Representative histological micrographs of the mammary glands 10 days after treatment with (i) PBS; (ii) TNP-8 at a dose of 2 mg/kg; (iii) TNP-8 at a dose of 6 mg/kg; (iv) TNP-8 at a dose of 8 mg/kg. Cell shedding and barrier loosening are noted; (v) Severe cell shedding into alveolar lumen is evident at a dose of 8 mg/kg; (vi) An enlarged view of cell shedding. C. Representative histological micrographs of the mammary glands 10 days after treatment with (i) TNP-50 at a dose of 2 mg/kg; (ii) TNP-50 at a dose of 6 mg/kg; (iii) TNP-50 at a dose of 8 mg/kg; (iv) Cell shedding into alveolar lumen is observed at a dose of 8 mg/kg. D. Quantification of numbers of mammary alveolar epithelial cells shed into the alveolar lumen. There were 7 mice in each experimental group and around 100 alveoli images were examined for each mouse. Scale bar: 40 μm; Narrow arrows indicate gap; Thick arrows indicate cell shedding.
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pone.0122591.g004: Shedding of mammary alveolar epithelial cells induced by TNPs.A. Schematic anatomical diagrams of lactating mammary glands during lactation period and cartoon indicates that ROS induced cell shedding. B. Representative histological micrographs of the mammary glands 10 days after treatment with (i) PBS; (ii) TNP-8 at a dose of 2 mg/kg; (iii) TNP-8 at a dose of 6 mg/kg; (iv) TNP-8 at a dose of 8 mg/kg. Cell shedding and barrier loosening are noted; (v) Severe cell shedding into alveolar lumen is evident at a dose of 8 mg/kg; (vi) An enlarged view of cell shedding. C. Representative histological micrographs of the mammary glands 10 days after treatment with (i) TNP-50 at a dose of 2 mg/kg; (ii) TNP-50 at a dose of 6 mg/kg; (iii) TNP-50 at a dose of 8 mg/kg; (iv) Cell shedding into alveolar lumen is observed at a dose of 8 mg/kg. D. Quantification of numbers of mammary alveolar epithelial cells shed into the alveolar lumen. There were 7 mice in each experimental group and around 100 alveoli images were examined for each mouse. Scale bar: 40 μm; Narrow arrows indicate gap; Thick arrows indicate cell shedding.
Mentions: Mammary alveolar epithelial cells are polarized secretory cells (Fig 4A). These cells synthesize milk proteins and secrete milk. There are tight junctions between the basal (blood) and apical (milk) sides of alveolar epithelial cells. The vital function of this barrier is to prohibit the direct paracellular exchange of substances between vascular and milk compartments during the lactation period. Because peak lactation in rodents occurs on LD 10, we first preformed histological examination of the integrity of mammary glands at LD 10 (Fig 4B–4D). The mammary glands of the lactating dams after PBS treatment contained intact alveolar epithelial cells. There was no noticeable cell shedding into the alveolar lumen (Fig 4Bi). After treatment with TNP-8 or TNP-50 at 2 mg/kg, the mammary glands showed no pathological alterations compared to the PBS group (Fig 4Bii for TNP-8 and Fig 4Ci for TNP-50). As the exposure dose increased, more shedding of epithelial cells into the alveolar lumen was observed (Fig 4Biii for TNP-8 and Fig 4Cii for TNP-50). Cell shedding became more severe when dams were exposed to a higher dose of TNP (Fig 4Biv and v for TNP-8 and Fig 4Ciii and iv for TNP-50). At the highest dose used (8 mg/kg), hyperplasia and stress-induced adipocytes were observed only for TNP-8 treatment (S3A and S3B Fig). The loss of mammary gland epithelial cells may produce defects or gaps in the tight junction of blood-milk barrier. By examining seven mice per exposure group and approximately 100 histological images for each mouse, we quantitatively determined the number of shed cells after each exposure. Our data showed that the smaller TNPs caused more cell shedding than the larger TNPs and cell shedding induced by both TNPs was dose-dependent (Fig 4D).

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