Chlorpyrifos exposure affects fgf8, sox9, and bmp4 expression required for cranial neural crest morphogenesis and chondrogenesis in Xenopus laevis embryos.
Chlorpyrifos (CPF) is an organophosphate insecticide used primarily to control foliage and soil-borne insect pests on a variety of food and feed crops. In mammals, maternal exposure to CPF has been reported to induce dose-related abnormalities such as slower brain growth and cerebral cortex thinning. In lower vertebrates, for example, fish and amphibians, teratogenic activity of this compound is correlated with several anatomical alterations. Little is known about the effects of CPF on mRNA expression of genes involved in early development of the anatomical structures appearing abnormal in embryos. This study investigated the effects of exposure to different CPF concentrations (10, 15 and 20 mg/L) on Xenopus laevis embryos from stage 4/8 to stage 46. Some of the morphological changes we detected in CPF-exposed embryos included cranial neural crest cell (NCC)-derived structures. For this reason, we analyzed the expression of select genes involved in hindbrain patterning (egr2), cranial neural crest chondrogenesis, and craniofacial development (fgf8, bmp4, sox9, hoxa2 and hoxb2). We found that CPF exposure induced a reduction in transcription of all the genes involved in NCC-dependent chondrogenesis, with largest reductions in fgf8 and sox9; whereas, in hindbrain, we did not find any alterations in egr2 expression. Changes in the expression of fgf8, bmp4, and sox9, which are master regulators of several developmental pathways, have important implications. If these changes are confirmed to belong to a general pattern of alterations in vertebrates prenatally exposed to OP, they might be useful to assess damage during vertebrate embryo development. Environ. Mol. Mutagen. 57:589-604, 2016. © 2016 Wiley Periodicals, Inc.
Department of Biology, Università di Napoli "Federico II", Via Cinthia, 21, Napoli, 80126, Italy.
Margherita
M
Tussellino
Department of Biology, Università di Napoli "Federico II", Via Cinthia, 21, Napoli, 80126, Italy.
Raffaele
R
Ronca
Department of Biology, Università di Napoli "Federico II", Via Cinthia, 21, Napoli, 80126, Italy.
Rosa
R
Carotenuto
Department of Biology, Università di Napoli "Federico II", Via Cinthia, 21, Napoli, 80126, Italy.
Maria M
MM
Pallotta
Department of Biology, Università di Napoli "Federico II", Via Cinthia, 21, Napoli, 80126, Italy.
Maria
M
Furia
Department of Biology, Università di Napoli "Federico II", Via Cinthia, 21, Napoli, 80126, Italy. teresa.capriglione@unina.it.
Teresa
T
Capriglione
D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics; D004390:Chlorpyrifos / Q000633:toxicity*; D020219:Chondrogenesis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D009432:Neural Crest / Q000187:drug effects* / Q000196:embryology; D060888:Real-Time Polymerase Chain Reaction; D055758:SOX9 Transcription Factor / Q000235:genetics; D012886:Skull / Q000187:drug effects* / Q000196:embryology; D029867:Xenopus Proteins / Q000235:genetics*; D014982:Xenopus laevis
D055415:Bone Morphogenetic Protein 4; C576319:FGF8 protein, Xenopus; D055758:SOX9 Transcription Factor; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; D051524:Fibroblast Growth Factor 8; D004390:Chlorpyrifos
Xenopus laevis; chlorpyrifos; chondrogenesis; neural crest cell; neurodevelopmental toxicity; organophosphate pesticides