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卵母细胞生长对小鼠孤雌生殖胚胎植入前发育及组蛋白修饰的影响†

Effects of oocyte growth on development and histone modification during preimplantation in mouse parthenogenetic embryos†.

作者信息

Yamazaki Wataru, Higashiya Misako, Fujii Yuriko, Yano Megumi, Oikawa Takanori, Seki Shinsuke

机构信息

Animal Research Division, Bioscience Education and Research Support Center, Akita University, Akita, Japan.

Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.

出版信息

Biol Reprod. 2025 Aug 13;113(2):289-306. doi: 10.1093/biolre/ioaf114.

Abstract

Parthenogenetic embryos have two sets of genomes derived from fully grown oocytes (fg/fg) and are embryonically lethal by embryonic day 9.5 in mice. During growth phase, oocytes undergo epigenetic modifications, including DNA methylation and histone modification. A previous study demonstrated that parthenogenetic embryos derived from nongrowing oocytes (ng/ng) were arrested at the eight-cell stage. However, effects of growing-stage oocyte genomes (gr/gr) on dynamics of development and histone modifications in parthenogenetic embryos have not been fully elucidated. Here, we investigated the development and dynamics of global histone modifications during preimplantation in mouse parthenogenetic embryos derived from ng and gr oocytes. Severe developmental arrest at the two-cell stage was observed in ng/ng embryos. Developmental competence in gr/gr embryos gradually improved depending on donor oocyte diameter. Global histone modification levels of H3K4/9me3 were significantly decreased from early to late two-cell stages in gr/gr and fg/fg embryos, but were maintained in ng/ng embryos. We also investigated the global zygotic de novo transcriptional activity, and ng/ng embryos at the one- and two-cell stages showed comparable activity to that of fg/fg embryos. However, the transcript level of zygotic genome activation-related gene, zinc finger and SCAN domain containing 4 or Zscan4d (previously known as EG545913), was significantly low in ng/ng embryos at the late two-cell stage. This study describes the characteristics of global histone modifications during early preimplantation in ng/ng and gr/gr embryos, suggesting that oocyte genomes during early growth phase lead to developmental incompetence and disrupted histone modifications during preimplantation in parthenogenetic embryos.

摘要

孤雌生殖胚胎具有两套源自完全成熟卵母细胞(fg/fg)的基因组,在小鼠胚胎发育第9.5天时胚胎致死。在生长阶段,卵母细胞会经历表观遗传修饰,包括DNA甲基化和组蛋白修饰。先前的一项研究表明,源自未成熟卵母细胞(ng/ng)的孤雌生殖胚胎在八细胞阶段停滞发育。然而,生长阶段卵母细胞基因组(gr/gr)对孤雌生殖胚胎发育动态和组蛋白修饰的影响尚未完全阐明。在此,我们研究了源自ng和gr卵母细胞的小鼠孤雌生殖胚胎着床前阶段的发育情况以及整体组蛋白修饰的动态变化。在ng/ng胚胎中观察到在二细胞阶段出现严重的发育停滞。gr/gr胚胎的发育能力根据供体卵母细胞直径逐渐提高。在gr/gr和fg/fg胚胎中,从二细胞早期到晚期,H3K4/9me3的整体组蛋白修饰水平显著降低,但在ng/ng胚胎中保持不变。我们还研究了整体合子从头转录活性,ng/ng胚胎在一细胞和二细胞阶段的活性与fg/fg胚胎相当。然而,在二细胞晚期,ng/ng胚胎中合子基因组激活相关基因锌指和含SCAN结构域4或Zscan4d(以前称为EG545913)的转录水平显著较低。本研究描述了ng/ng和gr/gr胚胎着床前早期整体组蛋白修饰的特征,表明早期生长阶段的卵母细胞基因组导致孤雌生殖胚胎着床前发育无能和组蛋白修饰紊乱。

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