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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

Analysis of nutrient quality of milk in the lactating dams (A, B and C) and effects of TNP exposures to dams on developmental landmarks of pups during lactation period (D, E).(A) The mRNA levels of β-casein, lactoferrin, α-lactalbumin and epidermal growth factor in mammary gland tissue were analyzed at LD 10 by quantitative PCR assay after dosing of TNPs at 8 mg/kg to dams. Data are mean±sd. (n = 4) (B) Western blot of key milk proteins. (C) Bar graphs show relative levels of β-casein, lactoferrin, α-lactalbumin and epidermal growth factor by normalizing PBS group to 1.0. (D) Body weight gains of pups during the lactating period when dams were dosed with PBS, TNP-8 or TNP-50 (8 mg/kg BW) at LDs 2, 4, 6 and 8. (n = 7) (E) Effects of TNP treatments on key developmental landmarks of pups during lactation period. The symbol * represents significant difference from the PBS group (P<0.05).
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pone.0122591.g007: Analysis of nutrient quality of milk in the lactating dams (A, B and C) and effects of TNP exposures to dams on developmental landmarks of pups during lactation period (D, E).(A) The mRNA levels of β-casein, lactoferrin, α-lactalbumin and epidermal growth factor in mammary gland tissue were analyzed at LD 10 by quantitative PCR assay after dosing of TNPs at 8 mg/kg to dams. Data are mean±sd. (n = 4) (B) Western blot of key milk proteins. (C) Bar graphs show relative levels of β-casein, lactoferrin, α-lactalbumin and epidermal growth factor by normalizing PBS group to 1.0. (D) Body weight gains of pups during the lactating period when dams were dosed with PBS, TNP-8 or TNP-50 (8 mg/kg BW) at LDs 2, 4, 6 and 8. (n = 7) (E) Effects of TNP treatments on key developmental landmarks of pups during lactation period. The symbol * represents significant difference from the PBS group (P<0.05).

Mentions: Although, the positive control, CdCl2 (2 mg/kg), downregulated the transcription of the genes encoding β-casein, α-lactalbumin, lactoferrin, and EGF from quantitative PCR analysis (Fig 7A) as well as the expression of lactoferrin protein (Fig 7B and 7C), TNPs did not reduce the expression of key milk components at both mRNA and protein levels (Fig 7A–7C) when dams were exposed to TNPs at a dose of 8 mg/kg. These data indicated that the leakage of TNPs into milk did not deteriorate the nutrient quality of the milk. Milk supplies all of the nutrients required for neonatal growth [12], cognitive and psychosocial development [14], and immune defense [13]. Approximately 80–95% of the proteins in milk are synthesized in mammary alveolar epithelial cells [60]. The absence of a short-term negative effect of TNPs on the nutrient quality of milk was observed in this study. This result indicated that the TNPs had minimal effects on the synthesis of milk proteins even though they disrupted the blood-milk barrier.


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)

Analysis of nutrient quality of milk in the lactating dams (A, B and C) and effects of TNP exposures to dams on developmental landmarks of pups during lactation period (D, E).(A) The mRNA levels of β-casein, lactoferrin, α-lactalbumin and epidermal growth factor in mammary gland tissue were analyzed at LD 10 by quantitative PCR assay after dosing of TNPs at 8 mg/kg to dams. Data are mean±sd. (n = 4) (B) Western blot of key milk proteins. (C) Bar graphs show relative levels of β-casein, lactoferrin, α-lactalbumin and epidermal growth factor by normalizing PBS group to 1.0. (D) Body weight gains of pups during the lactating period when dams were dosed with PBS, TNP-8 or TNP-50 (8 mg/kg BW) at LDs 2, 4, 6 and 8. (n = 7) (E) Effects of TNP treatments on key developmental landmarks of pups during lactation period. The symbol * represents significant difference from the PBS group (P<0.05).
© Copyright Policy
Related In: Results  -  Collection

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pone.0122591.g007: Analysis of nutrient quality of milk in the lactating dams (A, B and C) and effects of TNP exposures to dams on developmental landmarks of pups during lactation period (D, E).(A) The mRNA levels of β-casein, lactoferrin, α-lactalbumin and epidermal growth factor in mammary gland tissue were analyzed at LD 10 by quantitative PCR assay after dosing of TNPs at 8 mg/kg to dams. Data are mean±sd. (n = 4) (B) Western blot of key milk proteins. (C) Bar graphs show relative levels of β-casein, lactoferrin, α-lactalbumin and epidermal growth factor by normalizing PBS group to 1.0. (D) Body weight gains of pups during the lactating period when dams were dosed with PBS, TNP-8 or TNP-50 (8 mg/kg BW) at LDs 2, 4, 6 and 8. (n = 7) (E) Effects of TNP treatments on key developmental landmarks of pups during lactation period. The symbol * represents significant difference from the PBS group (P<0.05).
Mentions: Although, the positive control, CdCl2 (2 mg/kg), downregulated the transcription of the genes encoding β-casein, α-lactalbumin, lactoferrin, and EGF from quantitative PCR analysis (Fig 7A) as well as the expression of lactoferrin protein (Fig 7B and 7C), TNPs did not reduce the expression of key milk components at both mRNA and protein levels (Fig 7A–7C) when dams were exposed to TNPs at a dose of 8 mg/kg. These data indicated that the leakage of TNPs into milk did not deteriorate the nutrient quality of the milk. Milk supplies all of the nutrients required for neonatal growth [12], cognitive and psychosocial development [14], and immune defense [13]. Approximately 80–95% of the proteins in milk are synthesized in mammary alveolar epithelial cells [60]. The absence of a short-term negative effect of TNPs on the nutrient quality of milk was observed in this study. This result indicated that the TNPs had minimal effects on the synthesis of milk proteins even though they disrupted the blood-milk barrier.

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