Translocation of (ultra)fine particles and nanoparticles across the placenta; a systematic review on the evidence of in vitro, ex vivo, and in vivo studies

Abstract

Fetal development is a crucial window of susceptibility in which exposure may lead to detrimental health outcomes at birth and later in life. The placenta serves as a gatekeeper between mother and fetus. Knowledge regarding the barrier capacity of the placenta for nanoparticles is limited, mostly due to technical obstacles and ethical issues. We systematically summarize and discuss the current evidence and define knowledge gaps concerning the maternal-fetal transport and fetoplacental accumulation of (ultra)fine particles and nanoparticles. We included 73 studies on placental translocation of particles, of which 21 in vitro/ex vivo studies, 50 animal studies, and 2 human studies on transplacental particle transfer. This systematic review shows that (i) (ultra)fine particles and engineered nanoparticles can bypass the placenta and reach fetal units as observed for all the applied models irrespective of the species origin (i.e., rodent, rabbit, or human) or the complexity (i.e., in vitro, ex vivo, or in vivo), (ii) particle size, particle material, dose, particle dissolution, gestational stage of the model, and surface composition influence maternal-fetal translocation, and (iii) no simple, standardized method for nanoparticle detection and/or quantification in biological matrices is available to date. Existing evidence, research gaps, and perspectives of maternal-fetal particle transfer are highlighted.

Fetotoxicity of Nanoparticles: Causes and Mechanisms

“…Direct particle translocation across the placental barrier has been considered as the most potential mechanisms underlying NP-induced fetotoxicity [ 117 ]. Previous studies demonstrated that CB NPs, CNTs, PS NPs, Si O 2 NPs [ 118 ], TiO 2 NPs [ 118 ], ZnO NPs [ 11 , 48 ], ZrO 2 NPs [ 18 , 119 ], CeO 2 NPs, Au NPs [ 120 , 121 , 122 ], Ag NPs, and quantum dots (QDs) [ 15 , 123 ] could cross the placental barrier and induce fetotoxicity.…”

“…Maternal NP exposure may induce fetotoxicity by the direct translocation of NPs to the fetus or indirect NP-induced maternal and placental mediators [ 37 , 38 , 117 ]. During the critical window of fetal development, the factors interfering with the whole process of gestation (maternal condition, placental function, and developing fetus), contribute to detrimental fetal outcomes.…”

A method for liquid spectrophotometric measurement of total and water-soluble iron and copper in ambient aerosols

“…Transition metals in ambient aerosols are emitted in a variety of chemical forms, such as metal oxides, metal sulfates, metal halides, metal organics and reactive nano-metalloid particles (Gonet and Maher, 2019;Sutto, 2018). Fe and Cu nanoparticles (< 0.1 µm) may be especially toxic due to unique surface properties, combined with their small sizes that allow them to pass through cellular membranes and ability to be translocated to other organs (Bongaerts et al, 2020;Lee et al, 2020;Moreno-Ríos et al, 2021). Water-soluble species are operationally defined and are obtained though aqueous dissolution of collected aerosols followed by liquid filtration of the extract solution (typical filter pore sizes of 0.22 or 0.45 µm), which is roughly analogous to the process particles undergo when deposited in the respiratory-tract-lining fluid.…”

Label-free detection of uptake, accumulation, and translocation of diesel exhaust particles in ex vivo perfused human placenta

“…A recent review by Bongaerts et al summarizes the current though scarce evidence on the maternal–fetal transfer and fetoplacental accumulation of (ultra)fine particles and nanoparticles [ 16 ]. Both wood smoke particles [ 17 ] and PM 2.5 (particulate matter ≤ 2.5 µm) [ 18 ] have been shown to accumulate in exposed placental first-trimester trophoblast cell lines (i.e., HTR-8/SVneo) at an applied dose of 0.5 µg/mL.…”