Zinc chelation and mullerian duct regression.

After observing that zinc chelation by EDTA (ethyldiamine tetraacetic acid) mimics Mullerian inhibiting substance (MIS)-induced regression of the Mullerian duct, a detailed morphological study of the effects of EDTA on the Mullerian duct was undertaken. Urogenital ridges from the 14-day-old fetal rat were incubated in medium containing EDTA for 14, 24, 38, 48, 62, and 72 hours. The tissues were then processed for light and electron microscopy and stained with antibodies to laminin, fibronectin, heparan sulfate, and type-IV collagen. EDTA simulates the regression produced by endogenous MIS, producing early loss of basement membrane integrity, loss of epithelial cell polarity and organization, and loss of recognizable duct integrity by 72 hours. Like MIS, EDTA has no effect on the Wolffian duct. In contrast to MIS-treated Mullerian ducts, however, those incubated with EDTA showed a different sequence of disappearance of basement membrane components, absence of the specific periductal mesenchymal condensation seen with MIS, and absence of epithelial cell migration into the mesenchyme. Zinc chelation may be part of a series of mechanistic steps involved in Mullerian duct regression.