Decreased expression of Wnt7a mRNA is inversely associated with the expression of estrogen receptor-alpha in human uterine leiomyoma

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 ge ne is also responsive to changes in the levels of sex steroid hormone in th e 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 an d the adjacent myometria. Of 30 cases of leiomyomas studied, 67% showed a d ecreased mRNA level as compared to the paired myometria. On the other hand, estrogen receptor-alpha (ER-alpha) mRNA is hyper-expressed in 67% of the l eiomyomas as compared to their paired myometrium. An inverse association at mRNA expression was found between Wnt7a and ER-alpha. Miller et al has sho wn that fetal exposure of DES results in de-regulation of Wnt7a during uter ine morphogenesis. Referring to their results, we have postulated that hype rsensitivity of leiomyoma cells to estrogen may deregulate the Wnt7a expres sion. Decreased expression of Wnt7a may lead to loss of control in patterni ng of the myometrium and result in development of leiomyoma.