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Sex Amphibian, Xenopus tropicalis, following Larval Exposure to an Aromatase Inhibitor
Citation:
OLMSTEAD, A. W., P. A. KOSIAN, J. J. KORTE, G. W. HOLCOMBE, K. WOODIS, AND S. J. DEGITZ. Sex Amphibian, Xenopus tropicalis, following Larval Exposure to an Aromatase Inhibitor. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, 91(2):143-150, (2009).
Impact/Purpose:
Results from this study demonstrate larval exposure to an aromatase inhibitor can result in the complete masculinization of females.
Description:
Aromatase is a steroidogenic enzyme that catalyzes the conversion of androgens to estrogens in vertebrates. Modulation of this enzyme’s activity by xenobiotic exposure has been shown to adversely affect gonadal differentiation in a number of diverse species. We hypothesized that exposure to the aromatase inhibitor, fadrozole, during the larval development of the tropical clawed frog, Xenopus tropicalis, would result in masculinization of the developing female gonad. Tadpoles were exposed to fadrozole at nominal concentrations from 1 to 64 µg/L in a flow-through chamber from <24 hours post-fertilization (NF stage 15-20) to metamorphosis (NF stage 66). At metamorphosis, morphologically-examined gonads indicated complete masculinization of all tadpoles at concentrations of 16 µg/L and above and a significant bias in sex ratio towards males at concentrations of 1 µg/L and above. No effects on metamorph times, body mass, or body length were observed. A subsample of frogs was randomly chosen to be raised to reproductive maturity (39 weeks post-fertilization) in control water. All frogs exposed as tadpoles to 16 µg/L fadrozole and above were phenotypic males (i.e. possessed testes) at sexual maturity. Intersexed gonads characterized by the presence of both testicular and ovarian tissue were observed in the 4 µg/L treatment. No differences in estradiol, testosterone, or vitellogenin plasma concentrations were observed in exposed males or females compared to controls. Females in the 4 µg/L treatment possessed a significantly greater percentage of pre-vitellogenic oocytes than controls and were significantly smaller in body mass. No differences in sperm counts were observed in exposed males compared to controls. Results from this study demonstrate larval exposure to an aromatase inhibitor can result in the complete masculinization of females. These masculinized females are phenotypically indistinguishable from normal males at adulthood. Lower levels of aromatase inhibition result in intersexed gonads and possible female reproductive impairment at adulthood.
