Testosterone Metabolism in the Estuarine Mysid Neomysis Integer (Crustacea; Mysidacea) Following Tributyltin Exposure

Abstract

Current evidence suggests that the biocide tributyltin (TBT) causes the development of imposex, a state of pseudohermaphrodism in which females exhibit functional secondary male characteristics, by altering the biotransformation or elimination of testosterone. Imposex in gastropods following TBT exposure is the most complete example of the effects of an endocrine disrupter on marine invertebrates. Previous studies have demonstrated that the estuarine mysid Neomysis integer converts testosterone into multiple polar and nonpolar metabolites resulting from both phase I and phase II biotransformations. In this study, the effects of TBT chloride (TBTCl) on the phase I and II testosterone metabolism of N. integer were evaluated. The TBTCl was highly toxic to N. integer (96-h median lethal concentration [LC50] of 164 ng/L). To assess the effects on testosterone metabolism, mysids were exposed for 96 h to different concentrations of TBTCl (control, 10, 100, and 1,000 ng/L), and testosterone elimination as polar hydroxylated, nonpolar oxido-reduced, and glucose- and sulfate-conjugated metabolites was examined. The TBTCl differentially affected testosterone metabolism. The effect of TBTCl on phase I metabolism was unclear and has been shown to vary among species, likely depending on the inducibility or presence of certain P450 isozyme families. Reductase activity and metabolic androgenization were induced in the 10-ng/L treatment, whereas higher concentrations resulted in a reduction of sulfate conjugation. The exact mechanisms underlying TBT-induced imposex and alterations in the steroid metabolism need to be further elucidated.

Mysid crustaceans as standard models for the screening and testing of endocrine-disrupting chemicals

“…In addition, in vivo metabolic studies with different substrates, such as the testosterone studies discussed above, could provide valuable tools for evaluating the effects of toxicant exposure, particularly when these can be linked with effects on higher levels of biological organization. From the in vivo testosterone metabolism studies with N. integer by Verslycke et al (2002Verslycke et al ( , 2003aVerslycke et al ( , 2004c, there is sufficient information to suggest that mysids can be useful models to evaluate potential chemical interaction with CYPmediated endogenous and exogenous metabolism.…”

“…Marine (10-20‰), >20°C yes Domingues et al, 1999;Reitsema and Neff, 1980 Holmesimysis costata (= Acanthomysis sculpta) Gorokhova, 2002;De Lisle and Roberts, 1994;Cuzin-Roudy and Saleuddin, 1989;Fockedey et al, 2006;Ghekiere et al, 2006a Energy metabolism; O:N ratio, C:N ratio Respiration, Biochemical composition, Crustacean hyperglycemic hormone McKenney 1998McKenney , 1999Roast et al, 1999b;Verslycke et al, 2003cVerslycke et al, , 2004dOECD, 2006;Chang, 2005 Embryonic development Greenwood et al, 1989;Wortham and Price, 2002;Fockedey et al, 2006;Ghekiere et al, 2006a Sexual maturatity, Time to first brood release, Egg development time ASTM, 1999;OECD, 2006 Sex ratio and intersexuality ASTM, 1999;OECD, 2006 Fecundity (brood size) ASTM, 1999;USEPA, 1995aUSEPA, , 1995bOECD, 2006Vitellogenesis Tuberty et al, 2002Ghekiere et al, 2004Ghekiere et al, , 2005Ghekiere et al, , 2006c Population dynamics Kuhn et al, 2000Kuhn et al, , 2001Raimondo and McKenney, 2005a Ecdysteroid metabolism, Ecdysteroid receptor interaction Cuzin-Roudy and Saleuddin, 1989;Yokota et al, 2005;Verslycke et al (unpublished data) Steroid metabolism Verslycke et al, 2002Verslycke et al, , 2003aVersl...…”

Testosterone metabolism in Neomysis integer following exposure to benzo(a)pyrene

“…Changes in testosterone metabolism in N. integer can be used to detect exposure to endocrine-disrupting chemicals (Verslycke et al, 2003(Verslycke et al, , 2004. In this study, mysids that were exposed for 96h to different B(a)P concentrations and subsequently for 6h to testosterone, were evaluated for their ability to eliminate testosterone as various metabolic derivatives.…”

“…A decrease in the elimination of testosterone as reduced or non polar metabolites was observed in the medium by mysids exposed to B(a)P when compared to solventcontrol, and The overall effect of B(a)P on the metabolic elimination of testosterone can be summarized by the metabolic androgenization ratio (MAR), calculated according to Baldwin et al (1997) and Verslycke et al (2003). The MAR is the ratio of the eliminated oxidoreduced derivatives to the eliminated hydroxylated and conjugated derivatives.…”

“…A number of studies have assessed steroid metabolism in several invertebrate model species. These studies provide novel insights into our understanding of steroid metabolic pathways among invertebrate phyla, but also evaluate species differences in their susceptibility to chemical disruption of steroid metabolism (Verslycke et al, 2003;Janer et al, 2005).…”