Abstract:
The human placenta is at the interface between maternal and fetal circulations, and is crucial for fetal development. The nanoparticles of cerium dioxide (CeO2 NPs) from air pollution are an unevaluated risk during pregnancy. Assessing the consequences of placenta exposure to CeO2 NPs could contribute to a better understanding of NPs\' effect on the development and functions of the placenta and pregnancy outcome. We used primary villous cytotrophoblasts purified from term human placenta, with a wide range of CeO2 NPs concentrations (0.1-101 μg/cm2) and exposure time (24-72 h), to assess trophoblast uptake, toxicity and impact on trophoblast differentiation and endocrine function. We have shown the capacity of both cytotrophoblasts and syncytiotrophoblasts to internalize CeO2 NPs. CeO2 NPs affected trophoblast metabolic activity in a dose and time dependency, induced caspase activation and a LDH release in the absence of oxidative stress. CeO2 NPs decreased the fusion capacity of cytotrophoblasts to form a syncytiotrophoblast and disturbed secretion of the pregnancy hormones hCG, hPL, PlGF, P4 and E2, in accordance with NPs concentration. This is the first study on the impact of CeO2 NPs using human primary trophoblasts that decrypts their toxicity and impact on placental formation and functions.
摘要:
人类胎盘位于母体和胎儿循环之间的界面,对胎儿发育至关重要。来自空气污染的二氧化铈(CeO2NPs)纳米颗粒在怀孕期间是一种未评估的风险。评估胎盘暴露于CeO2NPs的后果可能有助于更好地了解NPs对胎盘发育和功能以及妊娠结局的影响。我们使用了从足月人胎盘中纯化的原代绒毛滋养细胞,具有广泛的CeO2NPs浓度(0.1-101μg/cm2)和暴露时间(24-72h),为了评估滋养细胞的摄取,毒性和对滋养细胞分化和内分泌功能的影响。我们已经显示了细胞滋养细胞和合胞体滋养细胞内化CeO2NP的能力。CeO2NPs以剂量和时间依赖性影响滋养细胞代谢活性,在没有氧化应激的情况下诱导半胱天冬酶激活和LDH释放。CeO2NPs降低了细胞滋养细胞的融合能力,形成了合胞体滋养细胞,并干扰了妊娠激素hCG的分泌,hPL,PlGF,P4和E2,依照NPs浓度。这是使用人类主要滋养层对CeO2NPs的影响进行的第一项研究,该滋养层揭示了它们的毒性以及对胎盘形成和功能的影响。