title: Effects of androgen receptor mutation on testicular histopathology of patient having complete androgen insensitivity.
abstract: Androgens are required for normal male sex differentiation and development of male secondary sexual characteristics. Mutations in AR gene are known to cause defects in male sexual differentiation. In current study, we enrolled a 46,XY phenotypically female patient bearing testes in inguinal canal. DNA sequencing of the AR gene detected a missense mutation C.1715A > G (p. Y572C) in exon 2 which is already known to cause complete androgen insensitivity syndrome (CAIS). We focused on the effects of this mutation on the testicular histopathology of the patient. Surface spreading of testicular tissues showed an absence of spermatocytes while H&E staining showed that seminiferous tubules predominantly have only Sertoli cells. This meiotic failure is likely due to the effect of the AR mutation which ultimately leads to Sertoli cell only syndrome. Tubules were stained with SOX9 and AMH which revealed Sertoli cells maturation arrest. Western blot and realtime PCR data showed that patient had higher levels of AMH, SOX9 and inhibin-B in the testis. Therefore, we suggest that the dysfunctioning of AR by mutation enhances AMH expression which ultimately leads to the failure in maturation of Sertoli cells.
authors.affiliation: Molecular and Cell Genetics Laboratory, The CAS Key Laboratory of Innate Immunity and Chronic Diseases, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Collaborative Innovation Center of Genetics and Development, Collaborative Innovation Center for Cancer Medicine, Hefei, 230027, Anhui, China.|Prince Mutaib Chair for Biomarkers of Osteoporosis, Department of Biochemistry, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Ihtisham
authors.initials: I
authors.lastname: Bukhari
authors.affiliation: Department of Urology, The Fourth Affiliated Hospital, Anhui Medical University, Hefei, 230001, Anhui, China.
authors.forename: Guangyuan
authors.initials: G
authors.lastname: Li
authors.affiliation: Molecular and Cell Genetics Laboratory, The CAS Key Laboratory of Innate Immunity and Chronic Diseases, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Collaborative Innovation Center of Genetics and Development, Collaborative Innovation Center for Cancer Medicine, Hefei, 230027, Anhui, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Molecular and Cell Genetics Laboratory, The CAS Key Laboratory of Innate Immunity and Chronic Diseases, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Collaborative Innovation Center of Genetics and Development, Collaborative Innovation Center for Cancer Medicine, Hefei, 230027, Anhui, China.
authors.forename: Furhan
authors.initials: F
authors.lastname: Iqbal
authors.affiliation: Molecular and Cell Genetics Laboratory, The CAS Key Laboratory of Innate Immunity and Chronic Diseases, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Collaborative Innovation Center of Genetics and Development, Collaborative Innovation Center for Cancer Medicine, Hefei, 230027, Anhui, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Maternity and Child Health Hospital of Anhui Province, The Maternal and Child Health Clinical College, Anhui Medical University, Hefei, 230001, Anhui, China.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Maternity and Child Health Hospital of Anhui Province, The Maternal and Child Health Clinical College, Anhui Medical University, Hefei, 230001, Anhui, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Maternity and Child Health Hospital of Anhui Province, The Maternal and Child Health Clinical College, Anhui Medical University, Hefei, 230001, Anhui, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Fang
authors.affiliation: Prince Mutaib Chair for Biomarkers of Osteoporosis, Department of Biochemistry, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Nasser M
authors.initials: NM
authors.lastname: Al-Daghri
authors.affiliation: Molecular and Cell Genetics Laboratory, The CAS Key Laboratory of Innate Immunity and Chronic Diseases, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Collaborative Innovation Center of Genetics and Development, Collaborative Innovation Center for Cancer Medicine, Hefei, 230027, Anhui, China.|MRC Human Genetics Unit and Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Cooke
authors.affiliation: Molecular and Cell Genetics Laboratory, The CAS Key Laboratory of Innate Immunity and Chronic Diseases, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Collaborative Innovation Center of Genetics and Development, Collaborative Innovation Center for Cancer Medicine, Hefei, 230027, Anhui, China. zyuanwei@ustc.edu.cn.
authors.forename: Yuanwei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Molecular and Cell Genetics Laboratory, The CAS Key Laboratory of Innate Immunity and Chronic Diseases, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, University of Science and Technology of China, Collaborative Innovation Center of Genetics and Development, Collaborative Innovation Center for Cancer Medicine, Hefei, 230027, Anhui, China. biojxh@ustc.edu.cn.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000328:Adult; D013734:Androgen-Insensitivity Syndrome / Q000175:diagnosis* / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D006061:Gonadal Dysgenesis, 46,XY; D006801:Humans; D007265:Inhibins / Q000032:analysis; D008297:Male; D020125:Mutation, Missense; D011944:Receptors, Androgen / Q000235:genetics*; D018000:Receptors, Peptide / Q000032:analysis*; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis*; D055758:SOX9 Transcription Factor / Q000032:analysis; D012671:Seminiferous Tubules / Q000473:pathology; D012708:Sertoli Cells; D013090:Spermatocytes; D013737:Testis / Q000737:chemistry* / Q000473:pathology*
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C084621:anti-Mullerian hormone receptor; C422364:inhibin B; D007265:Inhibins
keywords: Androgen insensitivity syndrome; Androgen receptor; Cryptorchidism; Sertoli cell only