In utero diethylstilbestrol (DES) exposure alters Hox gene expression in the developing mullerian system

Diethylstilbestrol (DES) was widely used to treat pregnant women through 19 71, The reproductive tracts of their female offspring exposed to DES in ute ro are characterized by anatomic abnormalities, Here we show that DES admin istered to mice in utero produces changes in the expression pattern of seve ral Hox genes that are involved in patterning of the reproductive tract. DE S produces posterior shifts in Hox gene expression and homeotic anterior tr ansformations of the reproductive tract. In human uterine or cervical cell cultures, DES induces HOXA9 or HOXA10 gene expression, respectively, to lev els approximately twofold that induced by estradiol, The DES-induced expres sion is not inhibited by cyclohexamide, Estrogens are novel morphogens that directly regulate the expression pattern of posterior Hox genes in a manne r analogous to retinoic acid regulation of anterior Hox genes. Alterations in HOX gene expression are a molecular mechanism by which DES affects repro ductive tract development. Changes in Hox gene expression are a potential m arker for the effects of in utero drug use that may become apparent only at late stages of development.-Block, K., Kardana, A., Igarashi, P., Taylor, H. S. In utero diethylstilbestrol (DES) exposure alters Hox gene expression in the developing mullerian system.