Mullerian Inhibiting Substance (MIS) causes regression of the Mullerian ducts during a critical period in embryonic development in male mammals. In Persistent Mullerian Duct Syndrome (PMDS), an autosomal recessive trait in humans and dogs, the Mullerian ducts fail to regress in otherwise normal males. Previously we reported that PMDS-affected dogs produce bioactive testicular MIS postnatally. The purpose of the present study was to determine whether PMDS-affected canine embryos appropriately express MIS mRNA and protein during the critical period for Mullerian duct regression. Homozygous (PMDS-affected) and normal canine embryos were removed from timed pregnancies. Gonadal sex and the degree of Mullerian duct regression were determined from histologic sections. Positive immunohistochemical staining for MIS was found in testis sections of PMDS-affected and normal male embryos. A 1.8-kb MIS mRNA transcript was detected in testes of PMDS-affected males and normal male embryos and neonates. Furthermore, equal amounts of MIS mRNA transcript were detected in testes of PMDS-affected embryos and normal male littermates during the critical period for Mullerian duct regression. These data support a hypothesis of target organ resistance, such as an abnormality in the putative MIS receptor, as the etiology of the defect in this dog model.
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