Retinoic acid hydroxylation and teratogenesis in lake sturgeon (Acipenser fulvescens) from the St. Lawrence River and Abitibi region, Quebec
All-trans-retinoic acid (RA) is an extremely active form of vitamin A; however, excessive or insufficient concentrations elicit anomalies including those associated with limb and craniofacial development. Lake sturgeon (Acipenser fulvescens) from the St. Lawrence River and tributaries were estimated to have a 2.9% incidence of fin and craniofacial malformations. Among larvae raised in artificial streams, a greater incidence of fin malformations (6.3%; p < 0.001) occurred in St. Lawrence River sturgeon compared with larvae from the Abitibi region. To test the hypothesis that the differences in rate of malformations may be associated with metabolic imbalances of RA, cytochrome P-450 dependent conversion to 4-hydroxyretinoic acid (4-OH-RA) was investigated. Optimal assay conditions are described for in vitro 4-OH-RA production in liver microsomes. Enzyme activity tended to decrease with increasing age and gonadal development in fish collected from Abitibi, but no statistically significant effects of sex, age, length, or gonadal development were discerned. The rate of 4-OH-RA formation was 3.5-fold greater (p < 0.0001) in the St. Lawrence sturgeon while the concentrations of cytochrome P-450 inducing PCBs (expressed as dioxin toxic equivalents) were 20-fold greater in a composite liver sample of the St. Lawrence sturgeon. Liver retinoid concentrations were negatively correlated (p < 0.0001) with RA hydroxylation rate. These results are consistent with the possibility that cytochrome P-450 dependent RA metabolism increased by chemical contaminants is associated with developmental anomalies in the St. Lawrence sturgeon.