title: Nanoparticles can cross mouse placenta and induce trophoblast apoptosis.
abstract: BACKGROUND
  The effects of nanoparticles on pregnancy remain unclear. In this study, we investigate whether nanoparticles of a specific size can cross the placenta and affect trophoblast function.
  
  
  METHODS
  Fluorescently labelled carboxylate-modified polystyrene beads with diameters of 20, 40, 100, 200, and 500 nm were chosen as model particles. In vitro, trophoblast cell line (3A-Sub-E) or primary culture of term trophoblasts was used for nanoparticle uptake analysis using flow cytometry, confocal microscopy, BrdU proliferation assay and analysis of cell apoptosis using Western blot. Intravenous injection of nanoparticles into pregnant mice at embryonic day 17 was used to study whether nanoparticles can cross the placenta. The mouse placentas were collected and quantitatively analyzed using high-performance liquid chromatography for nanoparticle uptake.
  
  
  RESULTS
  Fluorescent polystyrene particles with diameters of up to 500 nm were taken up by the placenta and were able to cross the placental barrier. The fluorescent polystyrene particles were observed in various organs of fetuses after 4 h of administration to pregnant mice. The nanoparticle uptake by placental tissue was significantly increased in nanoparticles with a diameter of 40 nm. No linear association was evident between nanoparticle size and uptake. Nanoparticles with diameters of 20 nm (200 μg/ml) and 40 nm (500 μg/ml) could induce trophoblast cell apoptosis with increased cleaved caspase 3 and reduced cell proliferation.
  
  
  CONCLUSIONS
  Our findings suggest that nanoparticles can cross the placenta and be taken up by fetal organs. Certain concentrations of carboxylate-modified polystyrene nanoparticles may be cytotoxic to trophoblasts, which could alter placental function.
authors.affiliation: Division of High Risk Pregnancy, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Jian-Pei
authors.initials: JP
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Patrick C H
authors.initials: PC
authors.lastname: Hsieh
authors.affiliation: Division of High Risk Pregnancy, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Pathology, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Tao-Yeuan
authors.initials: TY
authors.lastname: Wang
authors.affiliation: Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Chen
authors.affiliation: Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Chang-Ching
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chen-Chun
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Division of High Risk Pregnancy, MacKay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan. Electronic address: cpchen@mmh.org.tw.
authors.forename: Chie-Pein
authors.initials: CP
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D010316:Particle Size; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism
keywords: Apoptosis; Nanoparticle; Placenta; Polystyrene bead; Trophoblast