S, T Shipman and LF Parada. 2000. A molecular basis for estrogen-induced
cryptorchidism. Developmental Biology 224:354-361.
epidemiological links between
and cryptorchidism in people
et al. demonstrate that maternal exposure to estrogens affects
a key part of the genetic control of testicular development, in a way
that would lead to impaired testicular descent for fetal males exposed
in the womb. This result provides a molecular mechanism through which
exposure to compounds with estrogenic properties would lead to cryptorchidism.
or failure of one or both testes to descend into the scrotum around birth,
is a common birth defect in infant boys, affecting about 3% of newborn
males. It can result in infertility and is associated with a pattern of
other testicular maladies (testicular dysgenesis syndrome).
with laboratory animals shows that cryptorchidism can be induced readily
through in utero exposure to anti-androgenic and estrogenic contaminants.
descent is regulated in two phases of fetal development. One of these
phases is controlled by androgens, the other by a hormone recently identified
as insulin-3. Male fetal mice developing without the insulin-3 gene (also called Insl3) have
did they do?
Nef et al. exposed pregnant mice to one of 3 different estrogenic
substances, 17a-estradiol, 17ß-estradiol
or DES. At several pre- and post-natal stages, embryos/pups were sacrificed
and examined to assess developmental condition and to determine whether
the treatments interfered with insulin-3 action.
did they find?
Male mice exposed in utero to the estrogenic substances developed
undescended testes. Molecular testing of the exposed vs. untreated mice
then confirmed that although the testes had differentiated normally and
that general patterns of DNA transcription were normal, insulin-3 transcription
"was severely altered." Further analysis indicated that insulin-3
gene expression was blocked in a key set of cells (Leydig cells) involved
in sending the hormonal signal controlling the second phase of testicular
descent. Thus the estrogenic substances blocked the expression of a
specific gene necessary for normal testicular descent.
study is important because it provides a molecular mechanism for the impact
of estrogenic compounds in producing cryptorchidism.