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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The endocannabinoid system and pivotal role of the CB_2 receptor in mouse spermatogenesis
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The endocannabinoid system and pivotal role of the CB_2 receptor in mouse spermatogenesis

机译：内源性大麻素系统和CB_2受体在小鼠精子发生中的关键作用

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摘要

The exact role of the endocannabinoid system (ECS) during spermatogenesis has not been clarified. We used purified germ cell fractions representative of all phases of spermatogenesis and primary cultures of spermatogonia. This approach allowed the precise quantification of the cannabinoid receptor ligands, anan-damide and 2-arachidonoylglycerol, and of the expression at transcriptional and transductional levels of their metabolic enzymes and receptors. Our data indicate that male mouse germ cells possess an active and complete ECS, which is modulated during meiosis, and suggest the presence of an autocrine endocannabinoid signal during spermatogenesis. Mitotic cells possess higher levels of 2-arachidonoylglycerol, which decrease in spermatocytes and spermatids. Accordingly, spermatogonia express higher and lower levels of 2-arachidonoylglycerol biosynthetic and degrading enzymes, respectively, as compared to meiotic and postmeiotic cells. This endocannabinoid likely plays a pivotal role in promoting the meiotic progression of germ cells by activating CB_2 receptors. In fact, we found that the selective CB_2 receptor agonist, JWH133, induced the Erk 1/2 MAPK phosphorylation cascade in spermatogonia and their progression toward meiosis, because it increased the number of cells positive for SCP3, a marker of meiotic prophase, and the expression of early meiotic prophase genes.
机译：尚不清楚内源性大麻素系统（ECS）在生精过程中的确切作用。我们使用了代表精子发生所有阶段和精原细胞原代培养物的纯化生殖细胞组分。这种方法可以精确定量大麻素受体配体，anan-damide和2-arachidonoylglycerol，以及它们的代谢酶和受体在转录和转导水平的表达。我们的数据表明，雄性小鼠生殖细胞具有活跃而完整的ECS，在减数分裂过程中受到调节，并暗示在精子发生过程中存在自分泌内源性大麻素信号。有丝分裂细胞具有较高水平的2-花生四烯酰基甘油，其在精母细胞和精子细胞中减少。因此，与减数分裂和减数分裂后的细胞相比，精原细胞分别表达较高和较低水平的2-花生四烯酰基甘油生物合成和降解酶。这种内源性大麻素可能通过激活CB_2受体在促进生殖细胞的减数分裂进程中起关键作用。事实上，我们发现选择性CB_2受体激动剂JWH133诱导了精原细胞中Erk 1/2 MAPK磷酸化级联并向减数分裂的方向发展，因为它增加了SCP3（减数分裂前期的标志物）和减数分裂前期基因的表达

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  • 作者

    Paola Grimaldi; Pierangelo Orlando; Sara Di Siena; Francesca Lolicato; Stefania Petrosino; Tiziana Bisogno; Raffaele Geremia; Luciano De Petrocellis; Vincenzo Di Marzo;

  • 作者单位

    Department of Public Health and Cellular Biology, University of Rome 'Tor Vergata', 00133 Rome, Italy;

    lnstitute of Protein Biochemistry (PO), Consiglio Nazionale delle Ricerche, via P. Castellino 111, Napoli, Italy Institutes of ,Institutes of Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche, via Campi Flegrei 34, Pozzuoli, Italy;

    Department of Public Health and Cellular Biology, University of Rome 'Tor Vergata', 00133 Rome, Italy;

    Department of Public Health and Cellular Biology, University of Rome 'Tor Vergata', 00133 Rome, Italy;

    Institutes of ,Institutes of Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche, via Campi Flegrei 34, Pozzuoli, Italy Institutes of ,Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, via Campi Flegrei 34, Pozzuoli, Italy;

    Institutes of ,Institutes of Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche, via Campi Flegrei 34, Pozzuoli, Italy Institutes of ,Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, via Campi Flegrei 34, Pozzuoli, Italy;

    Department of Public Health and Cellular Biology, University of Rome 'Tor Vergata', 00133 Rome, Italy;

    Institutes of ,Institutes of Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche, via Campi Flegrei 34, Pozzuoli, Italy Institutes of ,Institutes of Cybernetics, Consiglio Nazionale delle Ricerche, via Campi Flegrei 34, Pozzuoli, Italy;

    Institutes of ,Institutes of Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche, via Campi Flegrei 34, Pozzuoli, Italy Institutes of ,Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, via Campi Flegrei 34, Pozzuoli, Italy;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    cannabinoid receptors; meiosis; TRPV1;

    机译：大麻素受体减数分裂TRPV1;

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