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

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 (<i>N</i> = 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.

我们于妊娠第7、8、9天（gestation days, GDs）对孕鼠静脉注射10纳米银纳米颗粒（silver nanoparticles, AgNPs）或可溶性硝酸银（silver nitrate, AgNO₃），注射剂量为0（柠檬酸盐缓冲液对照组）或66微克银每只小鼠，以此探究银在孕鼠及胚胎/胎儿体内的分布情况。我们对妊娠第10天的对照组、AgNPs处理组及硝酸银处理组孕鼠的选定母体组织与全部胚胎/胎儿，以及妊娠第16天的对照组和AgNPs处理组孕鼠的相关样本，开展了银浓度检测、细胞内AgNPs定位分析、组织病理学检查及组织形态大体观察。电感耦合等离子体质谱检测结果显示，经AgNPs或硝酸银处理后，所有受检组织中均检出银；其中母体肝脏、脾脏及内脏卵黄囊（visceral yolk sac, VYS）的银浓度最高，胚胎/胎儿体内银浓度最低。就内脏卵黄囊而言，硝酸银处理组的平均银浓度（4.87纳克银/毫克组织）约为AgNPs处理组（2.31纳克银/毫克组织）的2倍；其余所有受检组织中，AgNPs处理组与硝酸银处理组的平均银浓度均无显著差异（例如，AgNPs处理组与硝酸银处理组孕鼠肝脏的平均银浓度分别为2.57、2.84纳克银/毫克组织，脾脏分别为1.61、2.50纳克银/毫克组织）。高光谱成像结果显示，AgNPs处理组孕鼠的肝脏、肾脏、脾脏及内脏卵黄囊中存在AgNPs聚集物，而硝酸银处理组未检出此类聚集物。此外，10只接受AgNPs处理的孕鼠中，有8只的妊娠第10天胚胎存在1个或多个发育小于其胎龄的个体（即泰氏分期13期[GD8.5]或更早阶段）。对照组（样本量N=11）中，仅1只孕鼠的胚胎出现此类发育迟缓现象。综上，对孕鼠静脉注射10纳米AgNPs可导致银在母体肝脏、脾脏及内脏卵黄囊中显著蓄积，并可能影响胚胎发育；而胚胎/胎儿体内的银蓄积量可忽略不计。