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CNR1 基因敲除小鼠中低水平的 17β-雌二醇通过干扰染色体重组影响精子细胞染色质重塑。

Low 17beta-estradiol levels in CNR1 knock-out mice affect spermatid chromatin remodeling by interfering with chromatin reorganization.

机构信息

Dipartimento di Medicina Sperimentale, Sez Bottazzi, Seconda Università di Napoli, Napoli, Italy.

出版信息

Biol Reprod. 2013 Jun 20;88(6):152. doi: 10.1095/biolreprod.112.105726. Print 2013 Jun.

DOI:10.1095/biolreprod.112.105726
PMID:23677985
Abstract

The type 1-cannabinoid receptor, CNR1, regulates differentiation of spermatids. Indeed, we have recently reported that the genetic inactivation of Cnr1 in mice influenced chromatin remodeling of spermatids, by reducing histone displacement and then sperm chromatin quality indices (chromatin condensation and DNA integrity). Herein, we have studied, at both central and testicular levels, the molecular signals potentially involved in histone displacement. In particular, investigation of the neuroendocrine axis involved in estrogen production demonstrated down-regulation of the axis supporting FSH/estrogen secretion in Cnr1-knockout male mice. Conversely, Cnr1-knockout male mice treated with 17beta-estradiol showed a weak increase of pituitary Fsh-beta subunit mRNA levels and a rescue of sperm chromatin quality indices demonstrating that estrogens, possibly in combination with FSH secretion, play an important role in regulating chromatin remodeling of spermatids.

摘要

1 型大麻素受体,CNR1,调节精母细胞的分化。事实上,我们最近报道了 Cnr1 在小鼠中的基因失活影响了精母细胞的染色质重塑,通过减少组蛋白位移,然后降低精子染色质质量指数(染色质凝聚和 DNA 完整性)。在此,我们在中枢和睾丸水平上研究了潜在涉及组蛋白位移的分子信号。特别是,参与雌激素产生的神经内分泌轴的研究表明,在 Cnr1 敲除雄性小鼠中,支持 FSH/雌激素分泌的轴下调。相反,用 17β-雌二醇处理的 Cnr1 敲除雄性小鼠显示出垂体 Fsh-β亚基 mRNA 水平的微弱增加,并且精子染色质质量指数得到恢复,表明雌激素可能与 FSH 分泌一起,在调节精母细胞的染色质重塑中发挥重要作用。

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