Expression of anti-Mullerian hormone during normal and pathological gonadal development: Association with differentiation of Sertoli and granulosa cells
E. Rajpert-de Meyts et al., Expression of anti-Mullerian hormone during normal and pathological gonadal development: Association with differentiation of Sertoli and granulosa cells, J CLIN END, 84(10), 1999, pp. 3836-3844
The ontogeny of expression of anti-Mullerian hormone (AMH) was examined by
immunohistochemistry in 135 human gonadal tissue specimens of various devel
opmental age, ranging from 6 weeks of fetal development to 38 yr of postnat
al age. The series included specimens from normal testes and ovaries and fr
om individuals either with pathological conditions affecting gonadal develo
pment or with idiopathic infertility manifested as azoospermia or severe ol
igozoospermia. AMH expression was found only in Sertoli and granulosa cells
. A 6-week-old fetal testis at the indifferent gonad stage did not yet expr
ess AMH. The protein was first visible at 8.5 weeks of development, when se
x cords have not yet been formed. Afterward, a majority of testicular speci
mens, including those from pathological conditions, strongly expressed AMH
through fetal development and childhood until puberty. Markedly prolonged e
xpression of AMH was observed in a 20-yr-old 46,XY female with androgen ins
ensitivity syndrome, who retained prepubertal testicular morphology. In nor
mal testes, the switch-off of AMH expression was usually associated with th
e appearance of primary spermatocytes, suggesting that their presence had a
n inhibitory effect on AMH. However, in adolescent boys lacking germ cells
because of cancer treatment and in a majority of infertile adult men with i
diopathic germ cell aplasia, AMH expression was also down-regulated despite
the complete lack of spermatogenesis. The decrease in AMH expression thus
reflects the terminal differentiation of Sertoli cells and is probably only
partially dependent upon a regulatory factor associated with the onset of
meiosis. In fetal ovaries, AMH was first detected at 36 weeks gestation in
granulosa cells of preantral follicles. Thus, the onset of ovarian expressi
on is at the end of fetal life and not in infancy as previously reported.