Translocation of Engineered Nanomaterials from the Maternal Lungs to the Fetal Compartment After Instillation

Abstract

The majority of exposures to engineered nanomaterials (ENM) are unintentional through occupational or domestic use; however ENM biomedical platforms are being developed for use in individualized and/or tissue‐targeted treatments. The placenta has been described as a barrier organ, yet maternal treatments are limited during pregnancy to diminish untoward fetal effects and direct fetal therapies are rare. While negative maternal and fetal effects have been described after ENM exposure during gestation, it is unclear if these are due to direct ENM transfer into the fetal compartment or if the placental barrier protects the fetus from direct particle exposure. Therefore, the purpose of this study was to identify ENM translocation after maternal pulmonary exposure to the fetal compartment.Sprague‐Dawley rats were exposed to 2974 μg (2.4 × 1013 particles; calculated deposition of 952 ug/dose) of Rhodamine‐labeled 20nm polystyrene (NANOCS) in 300μL or saline control via intratracheal instillation every other day from GD 5 to GD 19. An acute group was also included, with a single ENM exposure on GD19. Animals were exposed to many optical imaging techniques (CT, FX‐Pro optical imaging, and ultrasound), in either the whole animal or dissected tissues on GD 20. Litter health was affected as evidenced by significantly higher rates of reabsorption sites in the exposed dams (18‐fold, chronic; 7‐fold, acute) compared to control. Overall, we were able to identify significantly higher optical intensity measurements in many secondary organs of the exposed animals, indicative of particle translocation from the lung. These included significantly increased optical imaging intensities in the chronic group vs the controls in the placenta (142% ± 78), whole fetal pup (144% ± 17), and in situ fetal liver (146% ± 13). Interestingly even those acutely exposed (24h prior) were also significantly different than control. These were identified as the mother's heart (156% ± 8), spleen (158% ± 6), placenta (142% ± 78), fetal heart (177% ± 37), fetal liver (both excised (190% ± 14) and within body (164% ± 10)), and whole pup (157% ± 13). Using novel placental perfusion methodology, where a placental unit is isolated, dissected, cannulated and perfused (80 mmHg maternal artery and 50 mmHg fetal umbilical artery), ENM introduced in the maternal artery can be quantified within 102 ± 13 minutes from the fetal umbilical vein effluent.Using molecular imaging techniques, we were able to conclusively identify ENM translocation from the maternal lungs to the fetal compartment. These findings may be both beneficial and toxicological depending on the purpose of the ENM exposure. ENM transfer to the fetal compartment may allow for direct fetal treatment with the use of ENM‐based biomedical devices; in contrast the placenta may not be considered a barrier to ENM, with direct fetal contact also occurring after unintentional maternal ENM exposures.Support or Funding InformationNIH‐R00‐ES024783 (PAS); P30‐ES005022This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.