Impact of chlorpyrifos on human villous trophoblasts and chorionic villi

Toxicol Appl Pharmacol. 2017 Aug 15:329:26-39. doi: 10.1016/j.taap.2017.05.026. Epub 2017 May 23.

Abstract

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.

Keywords: Basement membrane; Chlorpyrifos; Placental villi; Trophoblast cells; Xenobiotic transporters.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism
  • Apoptosis / drug effects
  • Basement Membrane / drug effects
  • Basement Membrane / ultrastructure
  • Biological Assay
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Chlorpyrifos / toxicity*
  • Cholinesterase Inhibitors / toxicity*
  • Chorionic Gonadotropin, beta Subunit, Human / metabolism
  • Chorionic Villi / drug effects*
  • Chorionic Villi / metabolism
  • Chorionic Villi / ultrastructure
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Insecticides / toxicity*
  • Neoplasm Proteins / metabolism
  • Pregnancy
  • Reproducibility of Results
  • Risk Assessment
  • Stromal Cells / drug effects
  • Stromal Cells / ultrastructure
  • Time Factors
  • Tissue Culture Techniques
  • Toxicity Tests / methods
  • Trophoblasts / drug effects*
  • Trophoblasts / metabolism
  • Trophoblasts / ultrastructure

Substances

  • ABCB1 protein, human
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Cholinesterase Inhibitors
  • Chorionic Gonadotropin, beta Subunit, Human
  • Insecticides
  • Neoplasm Proteins
  • Chlorpyrifos