Nanotoxicity to fetal brains after maternal oral exposures during pregnancy is often in question because nanoparticles have to cross multiple biological barriers such as intestinal barrier, maternal blood placental barrier (BPB) and fetal blood brain barrier (BBB). Here, we investigated this seemingly impossible passage for ZrO₂ nanoparticles (ZrO₂ NPs) from maternal body to fetal brains using a pregnant mouse model. After three oral exposures to pregnant mice at late pregnancy (GD16, 17, 18), ZrO₂ NPs were able to accumulate in fetal brains at GD19 via crossing the well-developed maternal BPB and fetal BBB. Moreover, ZrO₂ NPs crossed the mature biological barriers with increasing the expression levels of caveolae, clathrin and arf6 proteins as well as decreasing the expression levels of the tight junction proteins claudin-5, occludin and ZO-1 in placenta and fetal brain. From this investigation, we speculated that the main mechanisms for such translocation were receptor-mediated endocytosis transcellular pathway and breakthrough of tight junctions paracellular pathway in mature maternal BPB and fetal BBB. These findings have important implications for other nanoparticles exposures during pregnancy and provide crucial information to safeguard fetal development from contamination of widely used nanoproducts.

怀孕期间孕妇口服暴露后对胎儿大脑的纳米毒性通常是个问题，因为纳米颗粒必须穿越多种生物屏障，例如肠屏障，母体血胎盘屏障（BPB）和胎儿血脑屏障（BBB）。在这里，我们使用怀孕的小鼠模型研究了ZrO ₂纳米颗粒（ZrO ₂ NPs）从孕妇到胎儿大脑的这种看似不可能的传递。在怀孕晚期（GD16、17、18）对怀孕小鼠进行三次口服暴露后，ZrO ₂ NPs能够通过发育良好的母体BPB和胎儿BBB在GD19的胎儿脑中积累。此外，ZrO ₂NPs通过增加小窝，网格蛋白和arf6蛋白的表达水平以及降低胎盘和胎儿脑中紧密连接蛋白claudin-5，occludin和ZO-1的表达水平而跨越了成熟的生物学障碍。从这项调查，我们推测这种易位的主要机制是受体介导的内吞作用胞内通路和成熟母体BPB和胎儿BBB紧密连接旁细胞通路的突破。这些发现对怀孕期间其他纳米颗粒的暴露具有重要意义，并为保护胎儿发育免受广泛使用的纳米产品的污染提供了重要信息。