MAKING MALES FROM FEMALES - THE EFFECTS OF AROMATASE INHIBITORS ON A PARTHENOGENETIC SPECIES OF WHIPTAIL LIZARD

The parthenogenetic whiptail lizard Cnemidophorus uniparens provides a good model for the study of sex determination and sexual differentiat ion because genetic variation is minimal and all unmanipulated embryos will develop as females. Thus any deviation from the established cour se of development can be identified as a treatment effect. Previous wo rk has shown that early prenatal treatment with CGS16949A, a nonsteroi dal aromatase inhibitor, causes hatchlings to develop as males. The pr esent study explores more fully the effects of dosage and timing of ap plication of CGS16949A and examines the sex-reversing potential of CGS 20267, a new and reputedly more potent aromatase inhibitor. Eggs were treated with a range of dosages of the aromatase inhibitors. Hatchling s that received 1 mu g or more of either inhibitor were all male, whil e those that received 0.1 mu g or less were all female. No difference in potency between the two compounds was detected. Animals treated wit h 100 mu g of CGS16949A on Day 20 of incubation or later were all fema le, while those treated on Day 5 were all male. Seven sex-reversed mal e parthenogens have been raised to sexual maturity. The animals appear similar morphologically and behaviorally to males of the sexually rep roducing whiptail species. Spermatogenesis and spermiogenesis have bee n confirmed by histological examination of the testes and by postcopul atory cloacal swabs. Application of aromatase inhibitors has been show n to sex-reverse both avian and reptilian species. In mammals, the mal e-determining gene of the Y chromosome (SRY) may code for an intrinsic aromatase inhibitor. Studies show the gene's product has a binding do main which recognizes regulatory elements in the promoter of the aroma tase gene. These results suggest that the superficially different sex- determining processes of many amniotes may have underlying mechanisms in common. (C) 1995 Academic Press, Inc.