Tris(1,3-dichloro-2-propyl) Phosphate Exposure During the Early-Blastula Stage Alters the Normal Trajectory of Zebrafish Embryogenesis

Tris­(1,3-dichloro-2-propyl)
phosphate (TDCIPP) is an organophosphate
flame retardant used around the world. Within zebrafish, we previously
showed that initiation of TDCIPP exposure during cleavage (0.75 h
post-fertilization, hpf) results in epiboly disruption at 6 hpf, leading
to dorsalized embryos by 24 hpf, a phenotype that mimics the effects
of dorsomorphin (DMP), a bone morphogenetic protein (BMP) antagonist
that dorsalizes embryos in the absence of epiboly defects. The objective
of this study was to (1) investigate the role of BMP signaling in
TDCIPP-induced toxicity during early embryogenesis, (2) identify other
pathways and processes targeted by TDCIPP, and (3) characterize the
downstream impacts of early developmental defects. Using zebrafish
as a model, we first identified a sensitive window for TDCIPP-induced
effects following exposure initiation at 0.75 hpf. We then investigated
the effects of TDCIPP on the transcriptome during the first 24 h of
development using mRNA sequencing and amplicon sequencing. Finally,
we relied on whole-mount immunohistochemistry, dye-based labeling,
and morphological assessments to study abnormalities later in embryonic
development. Overall, our data suggest that the initiation of TDCIPP
exposure during early blastula alters the normal trajectory of early
embryogenesis by inducing gastrulation defects and aberrant germ-layer
formation, leading to abnormal tissue and organ development within
the embryo.