Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids

Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids
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DOI:
10.1242/dev.00957
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发表时间:
2004-01-01
期刊:
影响因子:
4.6
通讯作者:
Braun, RE
Braun, RE
中科院分区:
生物学2区
文献类型:
--
作者:
Holdcraft, RW;Braun, RE

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在哺乳动物中,雄激素受体的功能是雄性胚胎性别分化、青春期发育和精子发生调控所必需的。在精子发生过程中,这种需求被认为是由支持细胞介导的,其遗传和药理学破坏在精子细胞中表现为减数分裂停滞。通过对雄激素受体(Ar)基因的一个半形和条件等位基因的研究,我们发现了雄性生殖细胞分化过程中雄激素受体活性的双重减数分裂后需求。在Ar半形动物中的观察表明,精子的最终分化及其从精细胞上皮的释放依赖于Ar,并且对睾丸内Ar的耗尽最为敏感。在半形动物的支持细胞中,Ar的细胞特异性破坏进一步表明,后期圆形精子细胞向伸长步骤的进展对支持细胞Ar功能的丧失很敏感,但通过减数分裂和早期圆形精子细胞分化的进展却令人惊讶地不受影响。
Androgen receptor function is required for male embryonic sexual differentiation, pubertal development and the regulation of spermatogenesis in mammals. During spermatogenesis, this requirement is thought to be mediated by Sertoli cells and its genetic and pharmacological disruption is manifested in spermatocytes as meiotic arrest. Through studies of a hypomorphic and conditional allele of the androgen receptor (Ar) gene, we have uncovered a dual post-meiotic requirement for androgen receptor activity during male germ cell differentiation. Observations in Ar hypomorphic animals demonstrate that terminal differentiation of spermatids and their release from the seminiferous epithelium is AR dependent and maximally sensitive to AR depletion within the testis. Cell-specific disruption of Ar in Sertoli cells of hypomorphic animals further shows that progression of late-round spermatids to elongating steps is sensitive to loss of Sertoli cell AR function, but that progression through meiosis and early-round spermatid differentiation are surprisingly unaffected.