Gonadal structures in a fetus with complete androgen insensitivity syndrome and persistent Müllerian derivatives : comparison with normal fetal development

Objective: To report a case of complete androgen insensitivity syndrome (CAIS) with Müllerian duct persistence. Design: Case report. Setting: Academic hospital. Patient(s): A case of CAIS at 20 weeks' gestational age, and three male and one female 20-week-old fetuses for comparison. Intervention(s): DNA screening for androgen receptor (AR), antimüllerian hormone (AMH), and AMH receptor type 2 (AMHR2) gene mutations, and morphologic examination of Wolffian and Müllerian derivatives and immunohistochemistry for AMH, AMHR2, and bone morphogenetic protein receptor type 1A (BMPR1A) in aborted fetuses. Main Outcome Measure(s): Histopathologic, genetic, and immunohistochemical studies. Result(s): A novel mutation of AR (D767V) was identified in the index fetus. The CAIS case showed Wolffian duct degeneration, Leydig cell hyperplasia, and normally developed Sertoli cells. No AMH and AMHR2 gene sequence alterations were observed in the CAIS case, and the uterus and vagina were developed to a similar extent as found in the normal female 20-week-old fetus. The CAIS testes expressed more abundant AMH and showed fewer AMHR2-positive peritubular mesenchymal cells than the normal male testes, but BMPR1A stained similarly. Conclusion(s): Our study indicates that testes differentiation and development as well as the expression patterns of AMH, AMHR2, and BMPR1A are independent from AR function, at least up to the second trimester. The mechanisms by which the lack of functional androgen interferes with AMH action and Müllerian duct regression remain undefined.