Nanoparticle exposure in pregnancy may result in placental damage and fetotoxicity; however, the factors that determine fetal nanoparticle exposure are unclear. Here we have assessed the effect of gestational age and nanoparticle composition on fetal accumulation of maternally-administered nanomaterials in mice. We determined the placental and fetal uptake of 13 nm gold nanoparticles with different surface modifications (ferritin, PEG and citrate) following intravenous administration at E5.5-15.5. We showed that prior to E11.5, all tested nanoparticles could be visualized and detected in fetal tissues in significant amounts; however, fetal gold levels declined dramatically post-E11.5. In contrast, Au-nanoparticle accumulation in the extraembryonic tissues (EET) increased 6–15 fold with gestational age. Fetal and EET accumulation of ferritin- and PEG-modified nanoparticles was considerably greater than citrate-capped nanoparticles. No signs of toxicity were observed. Fetal exposure to nanoparticles in murine pregnancy is, therefore, influenced by both stage of embryonic/placental maturation and nanoparticle surface composition.

The materno-fetal transfer of nanoparticles is a critical issue in designing theranoustic nanoparticles for in vivo applications during pregnancy. Recent studies have reported that certain nanoparticles can cross the placental barrier in healthy pregnant animals depending on the size and surface modification of the nanoparticles and the developmental stages of the fetuses. However, materno-fetal transfer under pathological pregnant conditions has not been examined so far. Here, it is shown that intrauterine inflammation can enhance the materno-fetal transfer of nanoparticles in the late gestation stage of murine pregnancy in a size-dependent manner. Three different-sized gold nanoparticles (Au NPs) with diameters of 3 (Au3), 13 (Au13) and 32 (Au32) nm are applied. The accumulation of Au3 and Au13 nanoparticles in the fetuses is significantly increased in intrauterine inflammatory mice compared with healthy control mice: the concentration of Au3 is much higher than Au13 in fetal tissues of intrauterine inflammatory mice. In contrast, Au32 nanoparticles cannot cross the placental barrier either in healthy or in intrauterine inflammatory mice. The possible underlying mechanism of the increased materno-fetal transfer of small-sized nanoparticles on pathological conditions is inferred to be the structural and functional abnormalities of the placenta under intrauterine inflammation. The size of the nanoparticles is one of the critical factors which determines the extent of fetal exposure to nanoparticles in murine pregnancy under inflammatory conditions.

The active center of selenium-containing glutathione peroxidase (GPx) is selenocysteine (Sec), which is is biosynthesized on its tRNA in organisms. The decoding of Sec depends on a specific elongation factor and a Sec Insertion Sequence (SECIS) to suppress the UGA codon. The expression of mammalian GPx is extremely difficult with traditional recombinant DNA technology. Recently, a chimeric tRNA (tRNA) that is compatible with elongation factor Tu (EF-Tu) has made selenoprotein expression easier. In this study, human glutathione peroxidase (hGPx) was expressed in amber-less Escherichia coli C321.ΔA.exp using tRNA and seven chimeric tRNAs that were constructed on the basis of tRNA. We found that chimeric tRNA, which substitutes the acceptor stem and T-stem of tRNA with those from tRNA, enabled the expression of reactive hGPx with high yields. We also found that chimeric tRNA, which has a single base change (A59C) compared to tRNA, mediated the highest reactive expression of hGPx1. The hGPx1 expressed exists as a tetramer and reacts with positive cooperativity. The SDS-PAGE analysis of hGPx2 produced by tRNA with or without sodium selenite supplementation showed that the incorporation of Sec is nearly 90%. Our approach enables efficient selenoprotein expression in amber-less Escherichia coli and should enable further characterization of selenoproteins in vitro.