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Sexual differentiation is a sequential, ordered process. The genotype of the zygote determines the nature of the gonads, which leads to the development of either a male or female phenotype. In mammals, a gene for the putative testes-determining factor (TDF) has been identified on the Y chromosome (1, 2). This candidate TDF is related to the DNA-binding proteins HMG1 and HMG2 and to the product of the yeast gene Mc, a possible transcription factor. This suggests a role for TDF as the master switch for other genes downstream in the pathway of sexual differentiation. Whether a TDF homolog exists in birds remains to be determined.
Likely downstream targets for TDF include anti-Mullerian hormone (AMH) and the gonadal steroids. AMH causes regression of the embryonic Mullerian ducts and may act as a morphogen for testes development (3, 4). In addition, AMH may also regulate gonadal steroid hormone levels by inhibiting the enzyme aromatase (5). This enzyme catalyzes the final step in the biosynthesis of the gonadal steroids, that is, the conversion of androgens to estrogens. The gonadal steroids may participate in gonadal morphogenesis itself and are necessary for the development of male and female secondary sex characteristics. The ratio of estradiol to testosterone may also play a crucial role in sex determination because estrogen is known to attenuate the effects of AMH (3).
We used an aromatase inhibitor to evaluate the role of the gonadal steroids, specifically the conversion of testosterone to estradiol, in gonadal differentiation of the early chicken embryo. We treated embryos with 1 mg of the aromatase inhibitor (+/-)5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazo[1,5-alpha] pyridine hydrochloride (AI) on day 5 of egg incubation to test whether aromatase inhibition is crucial in controlling gonadal differentiation (6, 7). This caused essentially 100% (Table 1) of all hatchlings to vent sex as males (8). (Table 1 omitted) Vent sexing exploits the dimorphism in the cloaca to determine phenotypic sex shortly after hatching (9). Doses of 0.01 mg were not effective (Table 1); doses >=0.1 mg resulted in virtually all hatchlings developing a male phenotype (Table 1), but higher doses reduced hatching. Treatment was effective during a developmental window extending from preincubation (day 0) to day 7 of incubation (Table 1). The timing of treatment for successful sex reversal of females is...