Center for Bioenvironmental Research and Departments of Pharmacology (S.L., T.-C.C., R.M.W., V.P.W., J.A.M.), Tulane/Xavier Universities, and Department of Obstetrics and Gynecology (G.R.D.), Tulane University Medical Center, New Orleans, Louisiana 70112-2699
Abstract
Wnt-7a gene not only guides the development of the anterior-posterior
axis in the female reproductive tract, but also plays a critical role
in uterine smooth muscle pattering and maintenance of adult uterine
function. This gene is also responsive to changes in the levels of sex
steroid hormone in the female reproductive tract. To explore the
molecular mechanisms underlying the pathogenesis of uterine leiomyoma,
the expression of Wnt7a mRNA in the leiomyoma has been assessed. RT-PCR
was performed on uterine leiomyomas and the adjacent myometria. Of 30
cases of leiomyomas studied, 67% showed a decreased mRNA level as
compared to the paired myometria. On the other hand, estrogen
receptor- (ER-
) mRNA is hyper-expressed in 67% of the leiomyomas
as compared to their paired myometrium. An inverse association at mRNA
expression was found between Wnt7a and ER-
. Miller et alhas shown that fetal exposure of DES results in de-regulation of
Wnt7a during uterine morphogenesis. Referring to their results, we have
postulated that hypersensitivity of leiomyoma cells to estrogen may
deregulate the Wnt7a expression. Decreased expression of Wnt7a may lead
to loss of control in patterning of the myometrium and result in
development of leiomyoma