Aromatase inhibitors administered before sexual differentiation of the gona
ds can induce sex reversal in female chickens. To analyze the process of se
x reversal, we have followed for several months the changes induced by Fadr
ozole, a nonsteroidal aromatase inhibitor, in gonadal aromatase activity an
d in morphology and structure of the female genital system. Fadrozole was i
njected into eggs on day four of incubation, and its effects were examined
during the embryonic development and for eight months after hatching.
In control females, aromatase activity in the right and the left gonad was
high in the middle third of embryonic development, and then decreased up to
hatching. After hatching, aromatase activity increased in the left ovary,
in particular during folliculogenesis, whereas in the right regressing gona
d, it continued to decrease to reach testicular levels at one month.
In treated females, masculinization of the genital system was characterized
by the maintenance of the right gonad and its differentiation into a testi
s, and by the differentiation of the left gonad into an ovotestis or a test
is; however, in all individuals, the left Mullerian duct and the posterior
part of the right Mullerian duct were maintained. In testes and ovotestes,
aromatase activity was lower than in gonads of control females (except in t
he right gonad as of one month after hatching) but remained higher than in
testes of control and treated males. Moreover, in ovotestes, aromatase acti
vity was higher in parts displaying follicles than in parts devoid of folli
cles. The main structural changes in the gonads during sex reversal were pa
rtial (in ovotestes) or complete (in testes) degeneration of the cortex in
the left gonad, and formation of an albuginea and differentiation of testic
ular cords/tubes in the two gonads. Testicular cords/tubes transdifferentia
ted from ovarian medullary cords and lacunae whose epithelium thickened and
became Sertolian. Transdifferentiation. occurred all along embryonic and p
ostnatal development; thus, new testicular cords/tubes were continuously fo
rmed while others degenerated. The sex reversed gonads were also characteri
zed by an abundant fibrous interstitial tissue and abnormal medullary conde
nsations of lymphoid-like cells; in the persisting testicular cords/tubes,
spermatogenesis was delayed and impaired. Related to aromatase activity, pe
rsistence of too high levels of estrogens can explain the presence of ovidu
cts, gonadal abnormalities and infertility in sex reversed females. J. Exp.
Zool. 290:727-740, 2001. (C) 2001 Wiley-Liss, Inc.