Effects of androgen receptor mutation on testicular histopathology of patient having complete androgen insensitivity
Effects of androgen receptor mutation on testicular histopathology of patient having complete androgen insensitivity
复制标题
雄激素受体突变对雄激素完全不敏感患者睾丸组织病理学的影响
DOI：
10.1007/s10735-017-9714-7
复制
发表时间：
2017-06-01
影响因子：
3.2
通讯作者：
Jiang, Xiaohua
中科院分区：
文献类型：
--
作者：
Bukhari, Ihtisham;Li, Guangyuan;Jiang, Xiaohua
正常男性性别分化和男性第二性征的发育需要雄激素。已知 AR 基因突变会导致男性性别分化缺陷。在当前的研究中，我们招募了一名 46,XY 表型女性患者，其睾丸位于腹股沟管内。 AR基因的DNA测序检测到外显子2中存在错义突变C.1715A > G（p.Y572C），已知该突变会导致完全雄激素不敏感综合征（CAIS）。我们重点关注这种突变对患者睾丸组织病理学的影响。睾丸组织的表面扩散显示不存在精母细胞，而 H&E 染色显示生精小管主要仅含有支持细胞。这种减数分裂失败可能是由于 AR 突变的影响，最终导致仅支持细胞综合征。肾小管用 SOX9 和 AMH 染色，显示支持细胞成熟停滞。 Western blot 和实时 PCR 数据显示，患者睾丸中 AMH、SOX9 和抑制素 B 水平较高。因此，我们认为AR突变导致的功能障碍会增强AMH表达，最终导致支持细胞成熟失败。
Androgens are required for normal male sex differentiation and development of male secondary sexual characteristics. Mutations inARgene 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 theARgene 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 theARmutation 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 ofAMH, SOX9and inhibin-B in the testis. Therefore, we suggest that the dysfunctioning ofARby mutation enhances AMH expression which ultimately leads to the failure in maturation of Sertoli cells.