Increasing numbers of individuals may be exposed to nanomaterials during pregnancy. The overarching goal of this investigation was to determine if prenatal inhalation exposure to copper nanoparticles (Cu NPs) has an effect on dams and offspring, including an analysis of inflammatory markers (Th1/Th2 cytokine profiles). Physicochemical characterization of Cu NPs was performed. Pregnant and non-pregnant mice (C57Bl/6 J) were exposed to Cu NPs or laboratory air in the whole-body chamber for 4 hrs/day on gestation days (GD) 3–19 (3.5 mg/m3). Animals were euthanized on GD 19 (0 week) or 7 weeks later. Bronchoalveolar lavage (BAL) fluid was analyzed for total and differential cells. Cytokine/chemokine concentrations were determined in the BAL fluid and the plasma of dams/non-pregnant mice and pups. Cu content was determined in the lungs and the blood of dams/non-pregnant mice and pups, in the placentas as well as in the whole bodies of pups immediately after delivery. Lungs and placentas were evaluated for histopathological changes. Gene expression of the Th1/Th2 profiles were analyzed in spleens of pups. The survival rate of 7 week old pups exposed to Cu NPs was significantly lower than control pups (73 vs. 97 %). The average litter size, male/female ratio, body weight and lenght at birth were not different between Cu NP-exposed and control mice. Both pregnant and non-pregnant mice exposed to Cu NPs had significant pulmonary inflammation with increased number of neutrophils in the BAL fluid compared to controls. Perivascular lymphoplasmacytic cuffing was found in the lungs of exposed mice and was more pronounced in the non-pregnant group. Similarly, levels of inflammatory cytokines/chemokines IL-12(p40), G-CSF, GM-CSF, KC, MCP-1, MIP-1α, MIP-1β, RANTES and TNF-α in BAL fluid were significantly higher in non-pregnant than pregnant exposed mice. Histopathology evaluation of placentas did not identify any pathological changes. No translocation of Cu into the placenta or the fetus was found by inductively coupled plasma-mass spectroscopy. Expression of several Th1/Th2 or other immune response genes in pups’ spleens were found to be significantly up- or down-regulated. Prenatal exposure to Cu NPs caused a profound pulmonary inflammation in dams and strong immunomodulatory effects in offspring. There was no clear polarization of genes expressed in pups’ spleens towards Th1 or Th2 type of response.

中文翻译：

---

产前吸入铜纳米颗粒对鼠大坝和后代的影响。

在怀孕期间，越来越多的人可能会接触到纳米材料。这项研究的总体目标是确定产前吸入暴露于铜纳米颗粒（Cu NPs）是否对大坝和后代有影响，包括分析炎症标志物（Th1 / Th2细胞因子谱）。进行了铜纳米颗粒的理化表征。怀孕和未怀孕的小鼠（C57Bl / 6 J）在妊娠日（GD）3–19（3.5 mg / m3）的全室内暴露于铜纳米颗粒或实验室空气中，持续4小时/天。将动物在GD 19（0周）或7周后安乐死。分析了支气管肺泡灌洗液（BAL）的总细胞和分化细胞。测定BAL液和大坝/非妊娠小鼠和幼犬血浆中的细胞因子/趋化因子浓度。分娩后立即测定大坝/非妊娠小鼠和幼犬的肺，血液中的铜含量，以及胎盘中以及幼犬整个体内的铜含量。评估肺和胎盘的组织病理学变化。在幼犬的脾脏中分析了Th1 / Th2图谱的基因表达。暴露于铜纳米颗粒的7周龄幼崽的存活率显着低于对照幼崽（73对97％）。暴露于铜纳米粒的小鼠与对照组小鼠的平均产仔数，男女比例，出生时的体重和身长无差异。暴露于铜纳米颗粒的孕妇和非孕妇小鼠均具有明显的肺部炎症，与对照组相比，BAL液中的中性粒细胞数量增加。在裸露的小鼠的肺部发现了血管周淋巴胞质性套囊，在非妊娠组中更为明显。同样，非BAL液中炎性细胞因子/趋化因子IL-12（p40），G-CSF，GM-CSF，KC，MCP-1，MIP-1α，MIP-1β，RANTES和TNF-α的水平显着升高。 -比怀孕的暴露小鼠怀孕。胎盘的组织病理学评估未发现任何病理变化。电感耦合等离子体质谱法未发现Cu易位入胎盘或胎儿。发现幼鼠的脾脏中一些Th1 / Th2或其他免疫反应基因的表达明显上调或下调。产前暴露于铜纳米颗粒会在大坝中引起严重的肺部炎症，并对后代产生强烈的免疫调节作用。幼犬的脾脏中表达的基因对Th1或Th2型反应没有明显的极化。未怀孕的BAL液中的MIP-1α，MIP-1β，RANTES和TNF-α显着高于妊娠暴露的小鼠。胎盘的组织病理学评估未发现任何病理变化。电感耦合等离子体质谱法未发现Cu易位入胎盘或胎儿。发现幼鼠的脾脏中一些Th1 / Th2或其他免疫反应基因的表达明显上调或下调。产前暴露于铜纳米颗粒会在大坝中引起严重的肺部炎症，并对后代产生强烈的免疫调节作用。幼犬的脾脏中表达的基因对Th1或Th2型反应没有明显的极化。未怀孕的BAL液中的MIP-1α，MIP-1β，RANTES和TNF-α显着高于妊娠暴露的小鼠。胎盘的组织病理学评估未发现任何病理变化。电感耦合等离子体质谱法未发现Cu易位入胎盘或胎儿。发现幼鼠的脾脏中一些Th1 / Th2或其他免疫反应基因的表达明显上调或下调。产前暴露于铜纳米颗粒会在大坝中引起严重的肺部炎症，并对后代产生强烈的免疫调节作用。幼犬的脾脏中表达的基因对Th1或Th2型反应没有明显的极化。胎盘的组织病理学评估未发现任何病理变化。电感耦合等离子体质谱法未发现Cu易位入胎盘或胎儿。发现幼鼠的脾脏中一些Th1 / Th2或其他免疫反应基因的表达明显上调或下调。产前暴露于铜纳米颗粒会在大坝中引起严重的肺部炎症，并对后代产生强烈的免疫调节作用。幼犬的脾脏中表达的基因对Th1或Th2型反应没有明显的极化。胎盘的组织病理学评估未发现任何病理变化。通过电感耦合等离子体质谱法未发现Cu易位入胎盘或胎儿。发现幼鼠的脾脏中一些Th1 / Th2或其他免疫反应基因的表达明显上调或下调。产前暴露于铜纳米颗粒会在大坝中引起严重的肺部炎症，并对后代产生强烈的免疫调节作用。幼犬的脾脏中表达的基因对Th1或Th2型反应没有明显的极化。产前暴露于铜纳米颗粒会在大坝中引起严重的肺部炎症，并对后代产生强烈的免疫调节作用。幼犬的脾脏中表达的基因对Th1或Th2型反应没有明显的极化。产前暴露于铜纳米颗粒会在大坝中引起严重的肺部炎症，并对后代产生强烈的免疫调节作用。幼犬的脾脏中表达的基因对Th1或Th2型反应没有明显的极化。