MULLERIAN-INHIBITING SUBSTANCE IS PRESENT IN EMBRYONIC TESTES OF DOGSWITH PERSISTENT MULLERIAN DUCT SYNDROME

Mullerian Inhibiting Substance (MIS) causes regression of the Mulleria n ducts during a critical period in embryonic development in male mamm als. In Persistent Mullerian Duct Syndrome (PMDS), an autosomal recess ive trait in humans and dogs, the Mullerian ducts fail to regress in o therwise normal males. Previously we reported that PMDS-affected dogs produce bioactive testicular MIS postnatally. The purpose of the prese nt study was to determine whether PMDS-affected canine embryos appropr iately express MIS mRNA and protein during the critical period for Mul lerian duct regression. Homozygous (PMDS-affected) and normal canine e mbryos 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 se ctions of PMDS-affected and normal male embryos. A 1.8-kb MIS mRNA tra nscript was detected in testes of PMDS-affected males and normal male embryos and neonates. Furthermore, equal amounts of MIS mRNA transcrip t were detected in testes of PMDS-affected embryos and normal male lit termates during the critical period for Mullerian duct regression. The se data support a hypothesis of target organ resistance, such as an ab normality in the putative MIS receptor, as the etiology of the defect in this dog model.