Kanka J, Smith S D, Soloy E, Holm P, Callesen H
Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Libechov.
Mol Reprod Dev. 1999 Mar;52(3):253-63. doi: 10.1002/(SICI)1098-2795(199903)52:3<253::AID-MRD2>3.0.CO;2-N.
Nuclear transfer experiments in mammals have attempted to reprogram a donor nucleus to a state equivalent to the zygotic one. Reprogramming of the donor nucleus is, among other features, indicated by a synthesis of ribosomal RNA (rRNA). The initiation of rRNA synthesis is simultaneously reflected in nuclear morphology as a transformation of the nucleolus precursor body into a functional rRNA synthesising nucleolus with a characteristic ultrastructure. We examined nucleolar ultrastructure in bovine in vitro produced (control) embryos and in nuclear transfer embryos reconstructed from a MII phase (nonactivated) or S phase (activated) cytoplasts. Control embryos were fixed at the two-, four-, early eight- and late eight-cell stages; nuclear transfer embryos were fixed at 1 and 3 hr post fusion and at the two-, four-, and eight-cell stages. Control embryos possessed a nucleolar precursor body throughout all three cell cycles. In the eight-cell stage embryo, a primary vacuole appeared as an electron lucid area originating in the centre of the nucleolar precursor body. In nuclear transfer embryos reconstructed from nonactivated cytoplasts, the nuclear envelope was fragmented or completely broken down at 1 hr after fusion and, by 3 hr after fusion, it was restored again. At this time, the reticulated fibrillo-granular nucleolus had an almost round shape. The nucleolar precursor body seen in the two-cell stage nuclear transfer embryos consisted of intermingled filamentous components and secondary vacuoles. A nucleolar precursor body typical for the two-cell stage control embryos was never observed. None of the reconstructed embryos of this group reached the eight-cell stage. Nuclear transfer embryos reconstructed from activated cytoplasts, in contrast, exhibited a complete nuclear envelope at all time intervals after fusion. In the two-cell stage nuclear transfer embryo, the originally reticulated nucleolus of the donor blastomere had changed into a typical nucleolar precursor body consisting of a homogeneous fibrillar structure. A primary vacuole appeared in the four-cell stage nuclear transfer embryos, which was one cell cycle earlier than in control embryos. Only nuclear transfer embryos reconstructed from activated cytoplasts underwent complete remodelling of the nucleolus. The reorganisation of the donor nucleolar architecture into a functionally active nucleolus was observed as early as in the four-cell stage nuclear transfer embryo. These ultrastructural observations were correlated with our autoradiographic data on the initiation of RNA synthesis in nuclear transfer embryos.
哺乳动物的核移植实验试图将供体细胞核重编程至与合子细胞核相当的状态。供体细胞核的重编程在诸多特征中,可通过核糖体RNA(rRNA)的合成来体现。rRNA合成的起始同时在核形态学上表现为核仁前体转变为具有特征性超微结构的功能性rRNA合成核仁。我们研究了体外生产的(对照)牛胚胎以及由MII期(未激活)或S期(激活)细胞质体构建的核移植胚胎的核仁超微结构。对照胚胎在二细胞、四细胞、早期八细胞和晚期八细胞阶段固定;核移植胚胎在融合后1小时和3小时以及二细胞、四细胞和八细胞阶段固定。对照胚胎在所有三个细胞周期中均具有核仁前体。在八细胞期胚胎中,初级液泡表现为起源于核仁前体中心的电子透明区。在由未激活细胞质体构建的核移植胚胎中,核膜在融合后1小时破裂或完全解体,到融合后3小时又重新恢复。此时,网状纤维颗粒状核仁几乎呈圆形。在二细胞期核移植胚胎中看到的核仁前体由交织的丝状成分和次级液泡组成。从未观察到二细胞期对照胚胎典型的核仁前体。该组重构胚胎均未发育到八细胞期。相比之下,由激活细胞质体构建的核移植胚胎在融合后的所有时间间隔均表现出完整的核膜。在二细胞期核移植胚胎中,供体卵裂球原本的网状核仁已转变为由均匀纤维结构组成的典型核仁前体。初级液泡出现在四细胞期核移植胚胎中,比对照胚胎早一个细胞周期。只有由激活细胞质体构建的核移植胚胎经历了核仁的完全重塑。早在四细胞期核移植胚胎中就观察到供体核仁结构重组为功能活跃的核仁。这些超微结构观察结果与我们关于核移植胚胎中RNA合成起始的放射自显影数据相关。