Distribution and accumulation of 10 nm silver nanoparticles in maternal tissues and visceral yolk sac of pregnant mice, and a potential effect on embryo growth

Abstract

We examined the distribution of silver in pregnant mice and embryos/fetuses following intravenous injections of 10 nm silver nanoparticles (AgNPs) or soluble silver nitrate (AgNO3) at dose levels of 0 (citrate buffer control) or 66 µg Ag/mouse to pregnant mice on gestation days (GDs) 7, 8 and 9. Selected maternal tissues and all embryos/fetuses from control, AgNP- and AgNO3-treated groups on GD10 and control and AgNP-treated groups on GD16 were processed for the measurement of silver concentrations, intracellular AgNP localization, histopathology and gross examination of tissue morphology. Inductively-coupled plasma mass spectrometry revealed silver in all examined tissues following either AgNP or AgNO3 treatment, with highest concentrations of silver in maternal liver, spleen and visceral yolk sac (VYS), and lowest concentrations in embryos/fetuses. For VYS, mean silver concentration following AgNO3 treatment (4.87 ng Ag/mg tissue) was approximately two-fold that following AgNP treatment (2.31 ng Ag/mg tissue); for all other tissues examined, mean silver concentrations following either AgNP or AgNO3 treatment were not significantly different from each other (e.g. 2.57 or 2.84 ng Ag/mg tissue in maternal liver and 1.61 or 2.50 ng Ag/mg tissue in maternal spleen following AgNP or AgNO3 treatment, respectively). Hyperspectral imaging revealed AgNP aggregates in maternal liver, kidney, spleen and VYS from AgNP-treated mice, but not AgNO3-treated mice. Additionally, one or more embryos collected on GD10 from eight of ten AgNP-treated mice appeared small for their age (i.e. Theiler stage 13 [GD8.5] or younger). In the control group (N = 11), this effect was seen in embryos from only one mouse. In conclusion, intravenous injection of 10 nm AgNPs to pregnant mice resulted in notable silver accumulation in maternal liver, spleen and VYS, and may have affected embryonic growth. Silver accumulation in embryos/fetuses was negligible.

Disposition of intravenously or orally administered silver nanoparticles in pregnant rats and the effect on the biochemical profile in urine

“…The gestational/lactational translocation of particles has been demonstrated in rodents, including titanium dioxide (TiO 2 ) (Shimizu, et al 2009), diesel exhaust particles (Hemmingsen, et al 2009, Hougaard, et al 2008, Ramdhan, et al 2009), and fullerene C 60 (Snyder, et al 2015, Sumner, et al 2010a, Tsuchiya, et al 1996). A few studies have investigated the transfer of AgNP across the placenta in rats (Melnik, et al 2013) and mice (Austin, et al 2015, Austin, et al 2012, Wang, et al 2013). Following intravenous (i.v.)…”

“…Following intravenous (i.v.) administration of AgNP in pregnant mice, silver was detected in extra-embryonic tissues (visceral yolk sac, placenta, and endometrium), and embryos (Austin, et al 2015, Austin, et al 2012). Silver was also found the placenta and fetal tissues of mice following intraperitoneal administration of AgNP, and while the highest dosing concentration resulted in the highest recovered dose in the placenta, the lowest dose resulted in the highest detected silver concentrations in the embryo and fetal liver (Wang, et al 2013).…”

“…dosed mice (Austin, et al 2015, Austin, et al 2012, Wang, et al 2013) and p.o. dosed rats (Melnik, et al 2013), but a comprehensive examination of the role of NP size and route of delivery in distribution, internal dose, and persistence has not been presented previously.…”

Oocyte exposure to ZnO nanoparticles inhibits early embryonic development through the γ-H2AX and NF-κB signaling pathways

“…Concerns over the embryo-toxicity of nanoparticles (NPs) have increased exponentially over recent years and numerous articles have been published [1–71]. Many animal models have been used to test NPs embryo-toxicity; these include zebrafish [2–8, 10, 11, 14–17, 20–22, 24–28, 31, 33, 35, 37, 38, 41, 43, 45–47, 49–51, 53–57, 59, 62, 64, 66–70], mice [1, 9, 12, 13, 42, 48, 52, 63, 71], rat [18, 19, 30, 32], chicken [36, 44], oryzias latipes [23, 29, 34, 58], Xenopus laevis [7, 60], sea urchin [40] Mytilus galloprovincialis (Lmk) [39], snail [61], and oyster [65].…”

“…Many different types of NPs have been tested using these animal models. The most popular NPs are silver (Ag) NPs [1, 3, 8, 12, 13, 16, 22–26, 28, 32, 33, 34, 37, 38, 41, 43, 48, 49, 55, 56, 65, 66, 70], then zinc oxide (ZnO) NPs [3, 7, 14, 15, 18–20, 26, 40, 47, 62], gold (Au) NPs [3, 29, 30, 45, 46, 50–52, 55, 66, 67], titanium dioxide (TiO2) NPs [9, 16, 17, 21, 25, 28, 31, 39, 63, 69], silicon dioxide (SiO2) NPs [3, 26, 35, 58, 63], Cd NPs [3, 26, 53, 61], chitosan NPs [4, 42, 57], quantum tots [11, 60, 68], Cu NPs [25, 27, 64], platinium (Pt) NPs [44, 55] and other NPs including CoFe2O4, selenium, diamond, Ni, F2O3, and lead NPs [2, 5, 6, 10, 26, 27, 36, 45, 54, 59, 69, 71]. Although many articles have been published exploring the embryo-toxicity of NPs, only their toxic effects on different embryos have been investigated and very few studies have examined the underlying mechanisms.…”