Pleomorphic Adenoma Gene 1 Is Needed For Timely Zygotic Genome Activation and Early Embryo Development
Sci Rep. 2019 Jun 10;9(1):8411. doi: 10.1038/s41598-019-44882-0.
Madissoon E1, Damdimopoulos A2, Katayama S3, Krjutškov K4,5, Einarsdottir E3,5, Mamia K6, De Groef B7, Hovatta O6, Kere J8,9,10, Damdimopoulou P11,12.
Pleomorphic adenoma gene 1 (PLAG1) is a transcription factor involved in cancer and growth. We discovered a de novo DNA motif containing a PLAG1 binding site in the promoters of genes activated during zygotic genome activation (ZGA) in human embryos. This motif was located within an Alu element in a region that was conserved in the murine B1 element. We show that maternally provided Plag1 is needed for timely mouse preimplantation embryo development. Heterozygous mouse embryos lacking maternal Plag1 showed disrupted regulation of 1,089 genes, spent significantly longer time in the 2-cell stage, and started expressing Plag1 ectopically from the paternal allele. The de novo PLAG1 motif was enriched in the promoters of the genes whose activation was delayed in the absence of Plag1. Further, these mouse genes showed a significant overlap with genes upregulated during human ZGA that also contain the motif. By gene ontology, the mouse and human ZGA genes with de novo PLAG1 motifs were involved in ribosome biogenesis and protein synthesis. Collectively, our data suggest that PLAG1 affects embryo development in mice and humans through a conserved DNA motif within Alu/B1 elements located in the promoters of a subset of ZGA genes. PMID: 31182756 PMCID: PMC6557853 DOI: 10.1038/s41598-019-44882-0
Oocyte-expressed yes-associated protein is a key activator of the early zygotic genome in mouse
Cell Res. 2016 Mar;26(3):275-87. doi: 10.1038/cr.2016.20. Epub 2016 Feb 23.
Yu C1, Ji SY1, Dang YJ2, Sha QQ1, Yuan YF3, Zhou JJ1, Yan LY3, Qiao J3, Tang F2, Fan HY1.
In early mammalian embryos, the genome is transcriptionally quiescent until the zygotic genome activation (ZGA) which occurs 2-3 days after fertilization. Despite a long-standing effort, maternal transcription factors regulating this crucial developmental event remain largely elusive. Here, using maternal and paternal mouse models of Yap1 deletion, we show that maternally accumulated yes-associated protein (YAP) in oocyte is essential for ZGA. Maternal Yap1-knockout embryos exhibit a prolonged two-cell stage and develop into the four-cell stage at a much slower pace than the wild-type controls. Transcriptome analyses identify YAP target genes in early blastomeres; two of which, Rpl13 and Rrm2, are required to mediate maternal YAP's effect in conferring developmental competence on preimplantation embryos. Furthermore, the physiological YAP activator, lysophosphatidic acid, can substantially improve early development of wild-type, but not maternal Yap1-knockout embryos in both oviduct and culture. These observations provide insights into the mechanisms of ZGA, and suggest potentials of YAP activators in improving the developmental competence of cultured embryos in assisted human reproduction and animal biotechnology.
Analysis of human embryos from zygote to blastocyst reveals distinct gene expression patterns relative to the mouse
Dev Biol. 2012 Dec 19. pii: S0012-1606(12)00674-4. doi: 10.1016/j.ydbio.2012.12.008. [Epub ahead of print]
Niakan KK, Eggan K. Source The Howard Hughes Medical Institute, Harvard Stem Cell Institute and the Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA; Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, West Forvie Bldg, Robinson Way, Cambridge, CB2 0SZ, UK. Electronic address: email@example.com.
Mammalian embryogenesis is controlled by mechanisms governing the balance between pluripotency and differentiation. The expression of early lineage-specific genes can vary significantly between species, with implications for developmental control and stem cell derivation. However, the mechanisms involved in patterning the human embryo are still unclear. We analyzed the appearance and localization of lineage-specific transcription factors in staged preimplantation human embryos from the zygote until the blastocyst. We observed that the pluripotency-associated transcription factor OCT4 was initiated in 8-cell embryos at 3 days post fertilization (dpf) and is restricted to the inner cell mass (ICM) in 128-256 cell blastocysts (6dpf), approximately 2 days later than the mouse. The trophectoderm (TE)-associated transcription factor CDX2 was detectable in 5dpf blastocysts and initially coincident with OCT4, indicating a lag in CDX2 initiation and OCT4 repression in the TE lineage, relative to the mouse. Once established, the TE expressed intracellular and cell-surface proteins cytokeratin 7 and fibroblast growth factor receptor 1, which are thought to be specific to post-implantation human trophoblast progenitor cells. The primitive endoderm (PE)-associated transcription factor SOX17 was initially heterogeneously expressed in the ICM where it co-localized with a sub-set of OCT4 expressing cells at 4-5dpf. SOX17 was progressively restricted to the PE adjacent to the blastocoel cavity together with the transcription factor GATA6 by 6dpf. We observed low levels of Laminin expression in the human PE, though this basement membrane component is thought to play an important role in mouse PE cell sorting, suggesting divergence in differentiation mechanisms between species. Additionally, while stem cell lines representing the three distinct cell types that comprise a mouse blastocyst have been established, the identity of cell types that emerge during early human embryonic stem cell derivation is unclear. We observed that derivation from plating intact human blastocysts results predominantly in the outgrowth of TE-like cells, which impairs human embryonic stem cell derivation. Altogether, our findings provide important insight into developmental patterning of preimplantation human embryos with potential consequences for stem cell derivation. Copyright © 2012 Elsevier Inc. All rights reserved.
Barr body, polar bodies and Balbiani body; and the male sex body and chromatoid body.
Journal - Zygote Zygote An international journal dedicated to the rapid publication of original research in early embryology, Zygote covers interdisciplinary studies in animals and humans, from gametogenesis through fertilization to gastrulation.
Is pronuclear scoring a really good predictor for ICSI cycles?
Gynecol Endocrinol. 2010 Sep 1.
Aydin S, Cinar O, Demir B, Korkmaz C, Ozdegirmenci O, Dilbaz S, Goktolga U.
Center for Assisted Reproductive Medicine and IVF, Etlik Zubeyde Hanim Women's Health Teaching and Research Hospital, Ankara 06010, Turkey. Abstract Background/Aims. Since the assessments of the morphology of oocytes, zygotes and/or embryos are of crucial importance to select the best candidate for pregnancy, many morphological evaluation tools have been proposed. Although embryo scoring, particularly cleavage and blastocyst stages, is more convincing due to successful results, zygote scoring still have a bias as different outcomes. In the current study, we designed a prospective study to test the reliability of zygote scoring by focusing on zygote evaluation techniques and its relation with embryo development and embryo selection for transfer. Methods. A total of 1215 mature oocytes from 139 couples were evaluated for the study. Results. There is no correlation between published zygote scoring technique and embryo development. Conclusions. We conclude that the inconsistency of data obtained from zygote scoring might be caused by the static nature of pronuclear stage embryos and thus pronuclear scoring seems to be unreliable evaluation technique for embryo selection.
Number of blastomeres and distribution of microvilli in cloned mouse embryos during compaction
Zygote. 2010 Aug 25:1-6.
Li CB, Wang ZD, Zheng Z, Hu LL, Zhong SQ, Lei L.
Department of Histology and Embryology, Harbin Medical University, Harbin, China. Abstract SummaryThe events resulting in compaction have an important influence on the processes related to blastocyst formation. To analyse the quality of the embryos obtained by somatic cell nuclear transfer (SCNT) in aspects different from previous studies, not only the number of blastomeres of cloned embryos during the initiation of compaction, but also the distribution of microvilli in cloned, normal, parthenogenetic, and tetraploid embryos before and after compaction was preliminarily investigated in mouse. Our results showed that during compaction the number of blastomeres in SCNT embryos was fewer than that in intracytoplasmic sperm injection (ICSI) embryos and, before compaction, there was a uniform distribution of microvilli over the blastomere surface, but microvilli became restricted to an apical region after compaction in the four types of embryos. We also reported here that the time course of compaction in SCNT embryos was about 3 h delayed compared with that in ICSI embryos, while there was no significant difference between SCNT and ICSI embryos when developed to the 4-cell stage. We concluded that: (i) the cleavage of blastomeres in cloned embryos was slow at least before compaction; (ii) the distribution of microvilli in cloned, normal, parthenogenetic, and tetraploid embryos was coherent before and after compaction; and (iii) the initiation of compaction in SCNT embryos was delayed compared with that of ICSI embryos.
Association of distributions of three types of germinal vesicle stage oocytes with the canine follicle location in the ovary
Zygote. 2010 Jul 21:1-5. Wang LX, Wang S, Hou J, Hu RL, An XR.
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100094, China. Abstract SummaryThe objective of current study was to compare the nuclear configurations of canine oocytes recovered from between follicles after isolation. Follicles isolated were classified into follicle-S (follicles located in the ovarian surface) and follicle-I (follicles located inside the ovary) based on the follicle location in the ovary. Nuclear stages of canine oocytes recovered from follicle-S and follicle-I were examined by phase-contrast microscopy after isolation. Results demonstrated that canine GV stage oocytes can be classified into three types based on the status of the nuclear envelope, nucleolus, and chromatin: type A, type B, and type C. In follicle-S group, the majority (95.5%) of canine GV stage oocytes was of type B. All canine GV stage oocytes recovered from follicle-S (including type B and type C) were characterized by nuclear envelope disappearance prior to nucleolus collapse. In contrast, in follicle-I group, the majority (60.2%) of canine GV stage oocytes was of type C. Unexpectedly, a small proportion of canine GV stage oocytes from follicle-I (donated type A) were characterized by nuclear envelope disappearance following nucleolus collapse. In conclusion, nuclear configurations of each type of canine GV stage oocytes may differ from each other. Distributions of each type of canine GV stage oocytes may associate with the follicle location in the ovary.
Nucleologenesis and embryonic genome activation are defective in interspecies cloned embryos between bovine ooplasm and rhesus monkey somatic cells
Song BS, Lee SH, Kim SU, Kim JS, Park JS, Kim CH, Chang KT, Han YM, Lee KK, Lee DS, Koo DB. BMC Dev Biol. 2009 Jul 28;9:44. PMID 19635167
|Length of Gestation
(Data: Oklahoma State University Learning Reproduction in Farm Animals)
Fertilization - penetration of most ova during the first hour after ovulation.
- 0-16 h - pronuclei
- 16-22 h - 2 cell
- 22-29 h - 4 cell
- 29-32 h - 8 cell
- 32-77h - morula
- 77-98h - blastocyst
- 98h + - hatching blastocyst
|Species||Zygote||2 cell||4 cell||8 cell||Morula||Blastocyst||Hatching Blastocyst|
|Rabbit||0-16 h||16-22 h||22-29 h||29-32 h||32-77h||77-98h||98h +|
|Human||0-24 h||2 cell||4 cell||8 cell||76 h||96 h||120 h|
|Mouse||0-24 h||48 h||60 h||8 cell||72 h||96 h||Hatching Blastocyst|
|Species||Zygote||2 cell||4 cell||8 cell||Morula||Blastocyst||Hatching Blastocyst|
- Fertilized eggs, two-cell embryos, four-cell embryos, morulae, and blastocysts were collected [at 24, 48, 60, 72, and 96 hr
- 26 h (2-cell), 42 h (4-cell), 51 h (8-cell), 69 h (morula), and 91 h (blastocyst)