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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

The Ti content in pups’ GI tract and a cartoon presentation showing that TNPs cross the damaged tight junction entering the milk in lactating dams.(A) Ti content in pups’ GI tract at LD 10 after four doses of TNP exposures to lactating dams at LD 2, 4, 6 and 8. Symbol * represents significant difference from the PBS group (P<0.05). GI tract tissues from eight pups were collected per dam and pooled. There are five dams in each group. Data are mean±s.d. (B) A cartoon presentation showing that TNPs cross the damaged tight junction entering the milk in lactating dams.
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pone.0122591.g006: The Ti content in pups’ GI tract and a cartoon presentation showing that TNPs cross the damaged tight junction entering the milk in lactating dams.(A) Ti content in pups’ GI tract at LD 10 after four doses of TNP exposures to lactating dams at LD 2, 4, 6 and 8. Symbol * represents significant difference from the PBS group (P<0.05). GI tract tissues from eight pups were collected per dam and pooled. There are five dams in each group. Data are mean±s.d. (B) A cartoon presentation showing that TNPs cross the damaged tight junction entering the milk in lactating dams.

Mentions: Milk production and secretion are key functions of mammary glands. The disruption of tight junctions in mammary glands caused the transfer of small molecules from blood and interstitial spaces to milk [52]. It is intuitive that damage to the blood-milk barrier may also cause the transfer of TNPs from blood to milk. To demonstrate this transfer, it would be highly desirable to show the existence of TNPs in maternal milk. Technically, this experiment is very challenging because the tiny amount of secreted milk from a mouse is difficult to collect for ICP-MS analysis. Because milk is the only food source for newborn pups, TNPs may enter the pup’s GI tract through the milk feeding. To test this possibility, we analyzed the Ti content in pups’ GI tracts at LD 10 using ICP-MS (five dams per group, combined tissues from eight pups per dam). Our results demonstrated that Ti was accumulated in the GI tracts of the pups at LD 10 when TNP-8 particles were administered to the dams at a dose of 8 mg/kg (Fig 6A). In contrast, accumulation of Ti was not evident for larger TNP-50 or lower doses of TNP-8 particles. By analyzing Ti content in pups, we found that Ti content in GI tracts of pups is generally higher with a small standard deviation. Since the main activity of pups in lactation period was milk sucking, the probability of Ti transmission through random contamination from dam’s feces and urine was very low. The observed TNP-8 transfer from dams to pups during milk feeding at a maternal exposure dose of 8 mg/kg was consistent with the observed higher oxidative stress induction (Fig 3C) and tight junction damage (Figs 4B and 5B) by TNP-8 at this dose (Fig 6B). Nanoparticles have also been found to damage other biological barriers, such as the placental barrier [18, 53] and blood-testis barrier [20].


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)

The Ti content in pups’ GI tract and a cartoon presentation showing that TNPs cross the damaged tight junction entering the milk in lactating dams.(A) Ti content in pups’ GI tract at LD 10 after four doses of TNP exposures to lactating dams at LD 2, 4, 6 and 8. Symbol * represents significant difference from the PBS group (P<0.05). GI tract tissues from eight pups were collected per dam and pooled. There are five dams in each group. Data are mean±s.d. (B) A cartoon presentation showing that TNPs cross the damaged tight junction entering the milk in lactating dams.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4388820&req=5

pone.0122591.g006: The Ti content in pups’ GI tract and a cartoon presentation showing that TNPs cross the damaged tight junction entering the milk in lactating dams.(A) Ti content in pups’ GI tract at LD 10 after four doses of TNP exposures to lactating dams at LD 2, 4, 6 and 8. Symbol * represents significant difference from the PBS group (P<0.05). GI tract tissues from eight pups were collected per dam and pooled. There are five dams in each group. Data are mean±s.d. (B) A cartoon presentation showing that TNPs cross the damaged tight junction entering the milk in lactating dams.
Mentions: Milk production and secretion are key functions of mammary glands. The disruption of tight junctions in mammary glands caused the transfer of small molecules from blood and interstitial spaces to milk [52]. It is intuitive that damage to the blood-milk barrier may also cause the transfer of TNPs from blood to milk. To demonstrate this transfer, it would be highly desirable to show the existence of TNPs in maternal milk. Technically, this experiment is very challenging because the tiny amount of secreted milk from a mouse is difficult to collect for ICP-MS analysis. Because milk is the only food source for newborn pups, TNPs may enter the pup’s GI tract through the milk feeding. To test this possibility, we analyzed the Ti content in pups’ GI tracts at LD 10 using ICP-MS (five dams per group, combined tissues from eight pups per dam). Our results demonstrated that Ti was accumulated in the GI tracts of the pups at LD 10 when TNP-8 particles were administered to the dams at a dose of 8 mg/kg (Fig 6A). In contrast, accumulation of Ti was not evident for larger TNP-50 or lower doses of TNP-8 particles. By analyzing Ti content in pups, we found that Ti content in GI tracts of pups is generally higher with a small standard deviation. Since the main activity of pups in lactation period was milk sucking, the probability of Ti transmission through random contamination from dam’s feces and urine was very low. The observed TNP-8 transfer from dams to pups during milk feeding at a maternal exposure dose of 8 mg/kg was consistent with the observed higher oxidative stress induction (Fig 3C) and tight junction damage (Figs 4B and 5B) by TNP-8 at this dose (Fig 6B). Nanoparticles have also been found to damage other biological barriers, such as the placental barrier [18, 53] and blood-testis barrier [20].

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