Transcriptomics analysis of retinoic acid embryotoxicity in rat postimplantation whole embryo culture.
Rodent postimplantation whole embryo culture (WEC) is a classical alternative test to study developmental toxicants. Here, we have successfully applied transcriptomics to monitor early responses in WEC after exposure to the embryotoxicant retinoic acid (RA). We demonstrated that RA exposures ranging from 2 to 24h affect RA-responsive genes in individual embryos. Furthermore, 2, 3 or 4 somite embryos gave similar responses, allowing combining embryos of these embryonic stages within the same analysis. Microarray analysis of embryonic gene expression after RA exposure revealed the regulation of many genes known to be RA responsive. Finally, use of a culture medium based on bovine serum instead of rat serum yielded similar gene expression responses after RA exposure. These findings support the robustness of the identified gene expression patterns and show the feasibility of detecting early gene expression changes in WEC after embryotoxic exposures. This approach may result in a more sensitive readout for detecting embryotoxicity in WEC.
Luijten
Mirjam
M
Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Mirjam.Luijten@rivm.nl
van Beelen
Vincent A
VA
Verhoef
Aart
A
Renkens
Marc F J
MF
van Herwijnen
Marcel H M
MH
Westerman
Anja
A
van Schooten
Frederik-J
FJ
Pennings
Jeroen L A
JL
Piersma
Aldert H
AH
D000818:Animals; D046149:Embryo Culture Techniques / Q000379:methods*; D004622:Embryo, Mammalian / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005865:Gestational Age; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D013723:Teratogens / Q000633:toxicity*; D014212:Tretinoin / Q000633:toxicity*
D013723:Teratogens; D014212:Tretinoin