Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Andrology. 2013 May;1(3):421-30. doi: 10.1111/j.2047-2927.2013.00079.x. Epub 2013 Mar 28.
During the last phase of spermatogenesis, called spermiogenesis, the nucleosome-based chromatin structure is replaced by a protamine-based DNA packaging. Not much is known about the chromatin remodelling involved in humans and animals. Here, we have investigated initiation of chromatin remodelling over seven probands of which five were diagnosed with non-obstructive azoospermia (NOA) and two with obstructive azoospermia (OA) (failed vaso-vasostomy patients with proven fertility prior to vasectomy, Johnsen scores ≥9). Chromatin remodelling was studied evaluating the presence of nucleosomes, histone H3, pre-protamine 2 and protamine 1. This approach was feasible since the local initiation of nucleosome eviction in the sub acrosomal domain, which was visible in alkaline nuclear spread preparations. The patterns of nucleosome and H3 loss were largely congruent. Nucleus wide incorporation of protamine 1 could already be observed at the late round spermatid stage. Both for nucleosome loss and for protamine 1 incorporation, there was distinct variation within and between probands. This did not relate to the efficiency of sperm production per meiocyte. Pre-protamine 2 was always confined to the subacrosomal domain, confirming the role of this area in chromatin remodelling.
在精子发生的最后阶段,即精子形成阶段,核小体为基础的染色质结构被鱼精蛋白为基础的 DNA 包装所取代。关于涉及人类和动物的染色质重塑,我们知之甚少。在这里,我们研究了七个个体的染色质重塑的起始,其中五个被诊断为非梗阻性无精子症(NOA),两个为梗阻性无精子症(OA)(输精管结扎术前有生育能力的阻塞性无精子症患者,约翰森评分≥9)。通过评估核小体、组蛋白 H3、前鱼精蛋白 2 和鱼精蛋白 1 的存在来研究染色质重塑。由于在顶体下区可见核小体逐出的局部起始,这种方法是可行的,在碱性核展开制剂中可见到。核小体和 H3 丢失的模式在很大程度上是一致的。在晚期圆形精子细胞阶段,已经可以观察到鱼精蛋白 1 的全核整合。核小体丢失和鱼精蛋白 1 整合之间都存在明显的个体内和个体间的差异。这与每个减数分裂细胞的精子生成效率无关。前鱼精蛋白 2 始终局限于顶体下区,证实了该区域在染色质重塑中的作用。