High-throughput screening of toxicants that modulate extravillous trophoblast migration. (15th February 2023)

• Record Type: Journal Article
• Authors: Meakin, Cassandra; Kim, Christine; Lampert, Thomas; Aleksunes, Lauren M.
• Is Part Of: Toxicology letters. Volume 375(2023)
• Page Start: 1
• Page End: 7
• Publication Date: 2023-02-15
• Subjects: BPA bisphenol A -- BPB bisphenol B -- BPS bisphenol S -- CdCl2 cadmium chloride -- EGF epidermal growth factor -- EVT extravillous trophoblast -- PI propidium iodide -- RCD relative cell density -- TCP tricresyl phosphate -- TPP triphenyl phosphate -- TDCPP tris(1, 3-dichloro-2-propyl) phosphate -- ZEN zearalenone -- ZER zeranol -- α-ZOL α-zearalenol -- β-ZOL β-zearalenol; Extravillous trophoblast -- Migration -- Placenta -- Cadmium -- Bisphenol -- Zearalenone; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2022.12.004
• Languages: English
• ISSNs: 0378-4274

Abstract

Abstract: Migration and subsequent invasion of extravillous trophoblasts into the uterus is essential for proper formation of the placenta. Disruption of these processes may result in poor pregnancy outcomes including preeclampsia, placenta accreta, fetal growth restriction, or fetal death. Currently, there are several methods for quantifying cell migration and invasion in vitro, each with limitations. Therefore, we developed a novel, high-throughput method to screen chemicals for their ability to alter human trophoblast migration. Human HTR8/SVneo trophoblast cells were cultured in Oris™ cell migration plates containing stopper barriers. After EVT cells attached and chemicals were added to media, stoppers were removed thereby creating a cell-free detection zone for migration. Entry of trophoblasts into this zone was monitored through imaging every 6 h and used to calculate a relative cell density. Chemicals known to increase (epidermal growth factor) and decrease (pertussis toxin and cadmium) trophoblast migration were used to validate this in vitro method. Next, a panel of environmental chemicals including bisphenols, mycoestrogens, and flame retardants, were screened for their ability to alter trophoblast invasion. In conclusion, a real-time method to track extravillous trophoblast migration offers potential for screening contaminants as placental toxicants. Graphical Abstract: ga1 Highlights: Trophoblast entry into a cell-free zone can be monitored with real-time imaging. This migration assay can be used to screen potential human placenta toxicants. Cadmium chloride, bisphenols, and mycoestrogens reduce trophoblast migration. Organophosphate flame retardants increase trophoblast migration.