Abstract
BackgroundGold nanoparticles (AuNPs) have been widely studied for biomedical applications, although their safety and potential toxicity in pregnancy remains unknown. The aim of this study is to explore the effect of AuNPs maternal exposure at different gestational ages on fetal survival and development, as well as the potential mechanism of AuNPs affecting embryos and fetuses.MethodsThirty nm polyethylene glycol (PEG)-coated AuNPs (A30) were administered to pregnant mice via intravenous injection (5 μg Au/g body weight) over three days at either early or late pregnancy. Fetal abortion rate and morphological development in E16.5 were then detected in detail. The pregnant mice physiological states with A30 exposure were examined by biochemical, histological or imaging methods; and materno-fetal distribution of gold elements was assayed by electron microscopy and mass spectrometry. Murine embryonic stem cells derived embryoid-bodies or neuroectodermal cells were treated with A30 (0.0025 to 0.25 μg Au/mL) to examine A30 effects on expression levels of the germ differentiation marker genes. Tukey’s method was used for statistical analysis.ResultsExposure to A30 during early (A30E) but not late (A30L) pregnancy caused a high abortion rate (53.5%), lower fetal survival rate and abnormal decidualization compared with non-exposed counterparts. The developmental damage caused by A30 followed an “all-or-nothing” pattern, as the non-aborted fetuses developed normally and pregnancies maintained normal endocrine values. A30 caused minor impairment of liver and kidney function of A30E but not A30L mice. TEM imaging of fetal tissue sections confirmed the transfer of A30 into fetal brain and live as aggregates. qPCR assays showed A30 suppressed the expression of ectodermal, but not mesodermal and endodermal differentiation markers.ConclusionsThese results illustrate that maternal A30 exposure in early pregnant results in A30 transfer into embryonic tissues, inhibiting ectodermal differentiation of embryonic stem cells, leading to abnormal embryonic development and abortion. While exposure to A30 during late pregnancy had little or no impact on dams and fetuses. These findings suggest the safety of biomedical applications employing AuNPs during pregnancy is strongly influenced by fetal maturity and gestational age at exposure and provide the clues for AuNPs safe application period in pregnancy.
Highlights
With the rapid development of nanotechnology, a number of nanoparticles (NPs) have been approved for use in the medical, pharmaceutical and cosmetic fields (Bowman et al, 2010; Petros & DeSimone, 2010; Yang et al, 2012; Tian et al, 2013)
30 nm polyethylene glycol-coated AuNPs (A30) was administered via intravenous injection (i.v.) to pregnant mice over three days in the early or late pregnancy period to determine the effect of exposure to AuNPs on fetal development at different gestational ages
We showed that exposure to A30 during early pregnancy, which corresponds to the first trimester of human pregnancy, resulted in a significant increase in the rate of abortions and stillbirths, but does not lead to obvious developmental deficits in surviving offspring
Summary
With the rapid development of nanotechnology, a number of nanoparticles (NPs) have been approved for use in the medical, pharmaceutical and cosmetic fields (Bowman et al, 2010; Petros & DeSimone, 2010; Yang et al, 2012; Tian et al, 2013). Exposure of AuNPs with different functional groups were reported to cause mortality, developmental disorders, hypolocomotor activity and abnormal behavioural activity of zebrafish embryos (Kim et al, 2013; Harper et al, 2011; Truong et al, 2012). Whether these in vitro studies could be extrapolated to the human situation remained uncertain, due in part to the significant impact of comparative placentation on the extent of fetal exposure (Aillon et al, 2009). The aim of this study is to explore the effect of AuNPs maternal exposure at different gestational ages on fetal survival and development, as well as the potential mechanism of AuNPs affecting embryos and fetuses
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