Retinoic acid isomers produce malformations in postembryonic development of the Japanese flounder, Paralichthys olivaceus.

Publisher: Zoological Society of Japan Country of Publication: Japan NLM ID: 8702287 Publication Model: Print Cited Medium: Print ISSN: 0289-0003 (Print) Linking ISSN: 02890003 NLM ISO Abbreviation: Zoolog Sci Subsets: MEDLINE

Original Publication: Tokyo, Japan : Zoological Society of Japan, c1984-

Flounder/*abnormalities ; Flounder/*growth & development ; Gene Expression Regulation, Developmental/*drug effects ; Tretinoin/*analogs & derivatives ; Tretinoin/*toxicity; Animals ; Animals, Newborn ; Bone Development/drug effects ; Isomerism ; Japan ; Jaw Abnormalities/chemically induced ; Phenotype ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptors, Calcitriol/genetics ; Receptors, Calcitriol/metabolism ; Receptors, Retinoic Acid/genetics ; Receptors, Retinoic Acid/metabolism ; Retinoid X Receptors ; Reverse Transcriptase Polymerase Chain Reaction ; Spine/abnormalities ; Spine/drug effects ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Tretinoin/chemistry

We previously reported that characteristic deformities were induced by retinoic acid (RA) treatment of the Japanese flounder, Paralichthys olivaceus, at 6-9 days post-hatching (dph). To evaluate the toxic potency of nuclear retinoid receptors in induction of deformities by RA, we here investigated the effects of retinoic acid isomers on postembryonic development of this species. Larvae were exposed to either 25 nM of all-trans RA (atRA), 9-cis RA (9cRA) or 13-cis RA (13cRA) at 6-9 dph. All RA isomers induced deformities in the lower jaw, caudal fin and vertebrae. In the lower jaw, growth retardation of the dentary was evident. In the vertebrae, the major abnormalities were hypertrophy of the centrum, central fusion, and an increase in the number of abdominal vertebrae. Caudal fin deformities included deformity of caudal bone complex and absence of the entire caudal fin. The absence of the hypural primordium at 12 dph was the first sign of abnormality in caudal fin development, and resulted in complete blocking of the caudal fin development. Among the RA isomers, atRA induced the most severe deformity in all skeletons examined. Retinoic acid receptor (RAR) expression was activated by atRA and 9cRA, and pitx2 expression was inhibited in the lower jaw by atRA and 9cRA. Vitamin D receptor (VDR) expression was specifically inhibited by atRA treatment, suggesting that RA inhibits the lower jaw growth by suppressing the expression of these genes. These results suggest that RA exerted toxic effects on the skeletal systems, mainly through the RAR pathway.

0 (RNA, Messenger)
0 (Receptors, Calcitriol)
0 (Receptors, Retinoic Acid)
0 (Retinoid X Receptors)
0 (Transcription Factors)
5688UTC01R (Tretinoin)

Date Created: 20021112 Date Completed: 20030411 Latest Revision: 20131121

20231215

10.2108/zsj.19.1105

12426472