The stages at which human fertilization arrests: microtubule and chromosome configurations in inseminated oocytes which failed to complete fertilization and development in humans
The stages at which human fertilization arrests: microtubule and chromosome configurations in inseminated oocytes which failed to complete fertilization and development in humans
复制标题
DOI：
10.1093/molehr/1.5.239
复制
发表时间：
1995-07-01
影响因子：
4
通讯作者：
Schatten, G.
中科院分区：
文献类型：
--
作者：
Asch, R.;Simerly, C.;Schatten, G.
受精的目标是一个，也只有一个，精子核与激活的卵母细胞内的雌性原核结合。为了成功地发生这一过程，必须发生几个事件，包括整个精子并入卵母细胞，伴随第二极体的挤出完成减数分裂成熟，先前静止的卵母细胞的代谢活化，精子核和母体染色体分别解凝聚成雄性和雌性原核，以及原核的细胞质迁移，使它们并置。这些事件中的任何一个缺陷对受精卵都是致命的，并可能被证明是不育的原因。在这项研究中，微管和DNA在受精的人类卵母细胞中成像，这些卵母细胞因未受精而被丢弃。掺入的精子尾部的存在和数量也使用对尾部中发现的但不是卵母细胞微管中发现的经冷冻后修饰的乙酰化-α-微管蛋白具有特异性的单克隆抗体记录。对58对患者夫妇的211个体外受精失败的卵母细胞进行了分析，确定了几个以前无法检测到的受精停滞期：（i）中期II停滞;（ii）精子成功结合后停滞;（iii）精子形成后停滞;（iv）有丝分裂细胞周期进展期间停滞;（iv）受精停滞。和（v）在减数分裂细胞周期进程中停滞。多精受精和胚胎发育停滞的数据也被提出。这些结果对男性和女性不孕症的诊断和治疗具有重要意义。他们也提供了合理使用卵胞浆内单精子注射（ICSI）治疗的理论基础，尽管他们认为这种方法会发现一些棘手的病例。人们对使用看似“未受精”但已受精的卵母细胞进行随后的再受精、ICSI甚至研究表示担忧，因为受精过程可能在精子穿透后停止。这些结果表明，父母的基因组的适当工会需要一系列的卵母细胞表面和卵母细胞内的细胞膜介导的事件，并在任何阶段的失败导致人类受精的逮捕。
The goal of fertilization is the union of one, and only one, sperm nucleus with the female pronucleus within the activated oocyte. For this to occur successfully, several events must transpire, including the incorporation of the entire spermatozoon into the oocyte, the completion of meiotic maturation with the extrusion of the second polar body, the metabolic activation of the previously quiescent oocyte, the decondensation of the sperm nucleus and the maternal chromosomes into the male and female pronuclei respectively, and the cytoplasmic migrations of the pronuclei, which bring them into apposition. Defects in any of these events are lethal to the zygote and might prove to be causes of infertility. In this study, the microtubules and DNA were imaged in inseminated human oocytes that had been discarded as unfertilized. The presence and number of incorporated sperm tails were also documented using a monoclonal antibody specific for the post-translationally modified acetylated-alpha-tubulin found in the tail, but not the oocyte, microtubules. An analysis of 211 oocytes from failed in-vitro fertilizations from 58 patient couples resulted in the determination of several previously undetectable phases at which fertilization arrests: (i) metaphase II arrest; (ii) arrest after the successful incorporation of the spermatozoon; (iii) arrest after the formation of the sperm aster; (iv) arrest during mitotic cell cycle progression; and (v) arrest during meiotic cell cycle progression. Data on polyspermy and arrested embryonic development are also presented. These results have implications for the diagnosis and treatment of female, as well as male, infertility. They also provide a rationale for the reasonable use of intracytoplasmic sperm injection (ICSI) therapy, although they suggest that cases intractable to this approach will be found. Concerns are raised about the use of seemingly 'unfertilized' but inseminated oocytes for subsequent re-inseminations, ICSI or even research, since the fertilization process might have arrested after sperm penetration. These results demonstrate that the proper union of the parental genomes requires a series of cytoskeletal-mediated events on the oocyte surface and within the oocyte proper, and that failure at any phase results in the arrest of human fertilization.