Putative molecular mechanism underlying sperm chromatin remodelling is regulated by reproductive hormones.
Putative molecular mechanism underlying sperm chromatin remodelling is regulated by reproductive hormones.
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DOI：
10.1186/1868-7083-4-23
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发表时间：
2012-12-17
影响因子：
5.7
通讯作者：
D'Souza S
中科院分区：
文献类型：
--
作者：
Gill-Sharma MK;Choudhuri J;Ansari MA;D'Souza S
雄性生殖激素在染色质凝聚的分子机制中的假定调节作用仍然知之甚少。在过去的十年中，我们建立了两个成年雄性大鼠模型，分别以20 mg/kg/d的环丙孕酮(CPA)15 天和3 mg/kg/d的氟奋乃静(FD)皮下注射60 d，造成睾酮或促性腺激素功能缺陷，影响体外精子染色质解聚的速度。这些大鼠模型已用于本研究，以描述睾酮和卵泡刺激素在精子染色质重塑的分子机制中的可能作用。我们报道，睾丸激素和促卵泡激素的缺乏都会影响多泛素化的组蛋白的周转，并导致它们在睾丸中积聚。睾酮功能缺陷降低了α、5-甲基帽结合核糖核酸结合蛋白(类似于小鼠的PIWI样果蝇蛋白PIWI/P元件诱导的Wimpy睾丸同源物)的表达，含有PaZ/Piwi-Argonaut-Zwille结构域和组蛋白脱乙酰酶1(HDAC1)、泛素连接酶(URE-B1/E3)、20S蛋白酶体MIW1伴随泛素激活酶(Ube1)、结合酶(Ube2d2)、染色域Y蛋白(Cdyl)、溴睾丸特异蛋白(BRDT)、hdac6(组蛋白去乙酰酶6)、雄激素依赖的同源盒胚胎蛋白(pem/RhoX5)等的表达。组蛋白h2b和th3(睾丸特异性h3)。FSH功能缺陷降低了睾丸cdyl和BRDT基因的表达，影响了泛素化的组蛋白的周转，阻碍了生理DNA修复机制，最终导致DNA损伤精子的受精。我们发现，睾丸激素和卵泡刺激素的缺乏通过“染色质缩合转录组和蛋白质组”的细微变化不同地影响了精子染色质的重塑过程，从而使“动态的”组蛋白被“惰性”的鱼精蛋白所替代，并改变了浓缩的精子染色质的表观遗传状态。染色质的不适当浓缩影响了精子染色质的细胞结构，这从CPA或FD处理的大鼠在体外与二硫苏糖醇孵育的未成熟附睾头精子核的微妙超微结构变化中可见一斑。
The putative regulatory role of the male reproductive hormones in the molecular mechanism underlying chromatin condensation remains poorly understood. In the past decade, we developed two adult male rat models wherein functional deficits of testosterone or FSH, produced after treatments with 20 mg/Kg/d of cyproterone acetate (CPA) per os, for a period of 15 days or 3 mg/Kg/d of fluphenazine decanoate (FD) subcutaneously, for a period of 60 days, respectively, affected the rate of sperm chromatin decondensation in vitro. These rat models have been used in the current study in order to delineate the putative roles of testosterone and FSH in the molecular mechanism underlying remodelling of sperm chromatin. We report that deficits of both testosterone and FSH affected the turnover of polyubiquitylated histones and led to their accumulation in the testis. Functional deficits of testosterone reduced expression of MIWI, the 5-methyl cap binding RNA-binding protein (PIWIlike murine homologue of the Drosophila protein PIWI/P-element induced wimpy testis) containing a PAZ/Piwi-Argonaut-Zwille domain and levels of histone deacetylase1 (HDAC1), ubiquitin ligating enzyme (URE-B1/E3), 20S proteasome α1 concomitant with reduced expression of ubiquitin activating enzyme (ube1), conjugating enzyme (ube2d2), chromodomain Y like protein (cdyl), bromodomain testis specific protein (brdt), hdac6 (histone deacetylase6), androgen-dependent homeobox placentae embryonic protein (pem/RhoX5), histones h2b and th3 (testis-specific h3). Functional deficits of FSH reduced the expression of cdyl and brdt genes in the testis, affected turnover of ubiquitylated histones, stalled the physiological DNA repair mechanism and culminated in spermiation of DNA damaged sperm. We aver that deficits of both testosterone and FSH differentially affected the process of sperm chromatin remodelling through subtle changes in the ‘chromatin condensation transcriptome and proteome’, thereby stalling the replacement of ‘dynamic’ histones with ‘inert’ protamines, and altering the epigenetic state of condensed sperm chromatin. The inappropriately condensed chromatin affected the sperm chromatin cytoarchitecture, evident from subtle ultrastructural changes in the nuclei of immature caput epididymal sperm of CPA- or FD-treated rats, incubated in vitro with dithiothreitol.
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DOI：
10.1002/(sici)1098-2795(200006)56:2
发表时间：
2000-06-01
影响因子：
2.5
作者：
Balhorn, R;Brewer, L;Corzett, M
通讯作者：
Corzett, M
影响因子：
6.6
作者：
Hazzouri, M;Pivot-Pajot, C;Rousseaux, S
通讯作者：
Rousseaux, S
影响因子：
3.6
作者：
Cho, C;Jung-Ha, H;Eddy, EM
通讯作者：
Eddy, EM
影响因子：
4.3
作者：
Boussouar, Faycal;Rousseaux, Sophie;Khochbin, Saadi
通讯作者：
Khochbin, Saadi
DOI：
10.1073/pnas.172511699
发表时间：
2002-10-15
影响因子：
11.1
作者：
Hook, SS;Orian, A;Eisenman, RN
通讯作者：
Eisenman, RN