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首页> 外文学位 >Retinoic acid receptor alpha in germ cells is important for mitosis of spermatogonia, spermatogonial differentiation and meiosis.
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Retinoic acid receptor alpha in germ cells is important for mitosis of spermatogonia, spermatogonial differentiation and meiosis.

机译：生殖细胞中的维甲酸受体α对于精原细胞的有丝分裂，精原细胞的分化和减数分裂很重要。

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摘要

Spermatogenesis is governed by vitamin A, as shown by vitamin A deficient (VAD) testes, which lack advanced germ cells. Vitamin A signaling is mediated by retinoid receptors. There are two families of retinoid receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs), each with alpha, beta and gamma subtypes. Retinoic acid receptor alpha (RARA), plays a significant role in the testis such that Rara-null males are infertile because of severe germ cell loss.;Striking similarities of the testicular phenotypes are detected between Rara-null and VAD mice: severely degenerated testes, lack of germ cells, sloughing of mature spermatids, and infertility. To discern the molecular function of RARA in germ cells, Rara was conditionally deleted using stimulated by retinoic acid 8 (STRA8)-iCRE. With RARA function disabled in germ cells, morphological abnormalities detected in the testes included lack of germ cell organization, lack of lumen, sloughing cells, and vacuolization. Not surprisingly, germ-cell specific Rara conditional knockout mice (cKO) had a dramatic reduction in epididymal sperm number. Further analysis of cKO testes demonstrated decreased spermatogonial proliferation and differentiation, while meiotic defects such as reduced synapsis, synaptonemal fragmentation, and unrepaired double strand breaks were increased. Furthermore, functional spermatogonial transplantation assays pointed to the possibility that RARA regulates spermatogonial stem cell colonization and proliferation, as shown by the reduction of donor-derived spermatogenesis from the cKO donor germ cells. The lack of RARA in the testes clearly shows quantifiable deficiencies during spermatogonial proliferation, differentiation, and meiosis.;Microarray gene expression studies of mRNAs from the enriched germ cells from wild type and cKO mice provided molecular evidence that RARA regulates spermatogonial differentiation at postnatal day 4 (P4) and meiosis at P8. Cell differentiation, cell adhesion, cell migration, and other pathways related to the early steps of spermatogonial differentiation were found to be functional categories significant in germ cells from P4. These were very distinct from synapsis, synaptonemal complex formation, and crossover formation related to meiosis, which were functional categories significant in germ cells from P8. In conjunction with phenotypic abnormalities, we provide gene expression evidence that RARA mediates retinoic acid function during spermatogonial proliferation, differentiation, and meiosis.
机译：精子发生受维生素A控制，如缺乏高级生殖细胞的维生素A缺乏症（VAD）睾丸所示。维他命A信号介导维生素A信号传导。有两个类视黄醇受体，视黄酸受体（RARs）和类视黄醇X受体（RXRs），每个家族都具有α，β和γ亚型。视黄酸受体α（RARA）在睾丸中起着重要作用，由于严重的生殖细胞丢失，使Rara-null雄性不育。;在Rara-null和VAD小鼠之间检测到睾丸表型的惊人相似之处：严重退化的睾丸，缺乏生殖细胞，成熟精子脱落和不育。为了辨别RARA在生殖细胞中的分子功能，使用视黄酸8（STRA8）-iCRE刺激有条件地删除了Rara。在生殖细胞中禁用RARA功能后，在睾丸中检测到的形态异常包括生殖细胞缺乏组织，管腔不足，细胞脱落和空泡形成。毫不奇怪，特定于生殖细胞的Rara条件敲除小鼠（cKO）的附睾精子数量显着减少。对cKO睾丸的进一步分析表明，精原细胞的增殖和分化减少，而减数分裂缺陷，如突触减少，突触断裂和未修复的双链断裂增加。此外，功能性精原细胞移植测定法指出了RARA调节精原干细胞定殖和增殖的可能性，这可通过减少来自cKO供体生殖细胞的供体来源的精子发生来证明。睾丸中缺乏RARA清楚地显示了精原细胞增殖，分化和减数分裂过程中可量化的缺陷。;来自野生型和cKO小鼠的丰富生殖细胞mRNA的微阵列基因表达研究提供了分子证据，证明RARA在产后第4天调节精原细胞的分化。 （P4）和P8的减数分裂。发现细胞分化，细胞粘附，细胞迁移以及与精原细胞分化早期步骤相关的其他途径是P4生殖细胞中重要的功能类别。这些与与减数分裂有关的突触，突触复合物形成和交换形成非常不同，它们是来自P8的生殖细胞中重要的功能类别。结合表型异常，我们提供了基因表达证据，表明RARA在精原细胞增殖，分化和减数分裂过程中介导视黄酸功能。

著录项

  • 作者

    Law, Sze Ming.;

  • 作者单位

    Washington State University.;

  • 授予单位 Washington State University.;
  • 学科 Molecular biology.;Histology.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 322 p.
  • 总页数 322
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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