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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.

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Acknowledgements

We are high thankful to the patients for cooperation during the study. This work was supported by the National Key Research and Developmental Program of China (2016YFC1000605), National Basic Research Program of China (2013CB945502), the National Natural Science Foundation of China (31501199, 31371519, 31571555 and 31601207), the Natural Science Foundation of China—Israel Science Foundation (31461143013-1183/14), Major Program of Development Foundation of Hefei Centre for Physical Science and Technology (2014FXZY003), the Fundamental Research Funds for the Central Universities (WK2340000069) and the Project of Cultivate Scientific Research Foundation of Fourth Affiliated Hospital of Anhui Medical University (F1407D). We are also highly thankful to Prince Mutaib Chair for Biomarkers of Osteoporosis, King Saud University for facilitation of this study.

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Correspondence to Yuanwei Zhang or Xiaohua Jiang.

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Ihtisham Bukhari and Guangyuan Li have contributed equally to this work.

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Bukhari, I., Li, G., Wang, L. et al. Effects of androgen receptor mutation on testicular histopathology of patient having complete androgen insensitivity. J Mol Hist 48, 159–167 (2017). https://doi.org/10.1007/s10735-017-9714-7

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Keywords

  • Cryptorchidism
  • Androgen insensitivity syndrome
  • Androgen receptor
  • Sertoli cell only