Ridano M E, Racca A C, Flores-Martin J B, Fretes R, Bandeira C L, Reyna L, Bevilacqua E, Genti-Raimondi S, Panzetta-Dutari G M
Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Universidad Nacional de Córdoba,CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Córdoba, Argentina.
Instituto de Investigaciones en Ciencias de la Salud (INICSA), Universidad Nacional de Córdoba, CONICET, Departamento de Histología y Embriología, Facultad de Medicina, Córdoba, Argentina.
Toxicol Appl Pharmacol. 2017 Aug 15;329:26-39. doi: 10.1016/j.taap.2017.05.026. Epub 2017 May 23.
Placental barrier regulates maternal-fetal interchange protecting the baby from damage caused by substances found in the uterine environment or circulating in the vascular system. Organophosphate (OP) pesticides are a paramount group of environmental pollutants used in intensive agriculture for protection against diseases and pests. While many studies have reported an increased risk of pregnancy alterations in pregnant women exposed to OPs, few have analyzed the effects caused by these pesticides in the placenta. Herein, we evaluated the effects of chlorpyrifos (CPF), one of the most widely used OP insecticides, on human placenta using in vitro and ex vivo exposure models. Villous cytotrophoblast cells isolated from normal human term placentas maintained their cell viability, differentiated into syncytiotrophoblast-like structures, and increased the expression of β-hCG, ABCG2, and P-gp in the presence of CPF at concentrations of 10 to 100μM. The same doses of CPF induced marked changes in chorionic villi samples. Indeed, CPF exposure increased stroma cell apoptosis, altered villi matrix composition, basement membrane thickness, and trophoblastic layer integrity. Histomorphological and ultrastructural alterations are compatible with those found in placentas where maternal-placenta injury is chronic and able to impair the placental barrier function and nutrient transport from mother to the fetus. Our study shows that placental ex vivo exposure to CPF produces tissue alterations and suggest that human placenta is a potential target of CPF toxicity. In addition, it highlights the importance of using different models to assess the effects of a toxic on human placenta.
胎盘屏障调节母胎物质交换,保护胎儿免受子宫环境中或血管系统中循环的物质所造成的损害。有机磷(OP)农药是集约化农业中用于防治病虫害的一类主要环境污染物。虽然许多研究报告了接触有机磷农药的孕妇发生妊娠改变的风险增加,但很少有研究分析这些农药对胎盘的影响。在此,我们使用体外和离体暴露模型评估了最广泛使用的有机磷杀虫剂之一毒死蜱(CPF)对人胎盘的影响。从正常足月人胎盘中分离出的绒毛细胞滋养层细胞在存在浓度为10至100μM的CPF时保持其细胞活力,分化为合体滋养层样结构,并增加了β-hCG、ABCG2和P-gp的表达。相同剂量的CPF在绒毛膜绒毛样本中引起了显著变化。事实上,CPF暴露增加了基质细胞凋亡,改变了绒毛基质组成、基底膜厚度和滋养层完整性。组织形态学和超微结构改变与在母胎胎盘损伤为慢性且能够损害胎盘屏障功能和从母亲到胎儿的营养物质转运的胎盘中发现的改变一致。我们的研究表明,胎盘离体暴露于CPF会产生组织改变,并表明人胎盘是CPF毒性的潜在靶点。此外,它强调了使用不同模型评估毒物对人胎盘影响的重要性。