Zygote

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Introduction

Early Human Zygote, with 2 pronuclei

The zygote is the first diploid cell that forms following fertilization by fusion of the haploid oocyte (egg) and spermatozoa (sperm) resulting in the combination of their separate genomes. The first image shows the cell with the 2 pronuclei still present before fusion enclosed within the zona pellucida. These two pronuclei contain the parental genomes and are reprogrammed separately, and also have different epigenetic changes at this early zygote stage.[1][2]


In humans, zygote stage of development occurs during the first day in week one following fertilization (GA week 3) and is described as Carnegie stage 1. This stage is followed by mitosis to form 2 blastomeres and then a solid cell mass called the morula.


Zygote Links: zygote Carnegie stage 1 | fertilization | Week 1 | morula | blastocyst | Assisted Reproductive Technology | SCNT | epigenetics | Category:Zygote


Stage 1 Links: Zygote | Week 1 | Oocyte | Spermatozoa | Zona pellucida | Mitosis | Genetics | Human Genome | Mitochondrial Genome | Lecture | Medicine Practical | Science Practical | Stage 2
Historic Papers  
1919 Human Ovum | 1944 Ova Maturation | 1944 In vitro fertilization | 1949 Early Ova | 1966 Pronuclear Stage | 1986 human oocytes in vitro

Some Recent Findings

  • Human embryos from zygote to blastocyst reveals distinct gene expression patterns relative to the mouse[3] "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. ...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."
  • cyclic AMP in the maturation of Ciona intestinalis oocytes[4] "Immature oocytes are arrested at prophase I of the meiotic process and maturation onset is indicated by oocyte nuclear disassembly (germinal vesicle breakdown or GVBD). Signaling pathways that elevate intracellular cyclic AMP (cAMP) may either prevent or induce oocyte maturation depending on the species."
  • Number of blastomeres and distribution of microvilli in cloned mouse embryos during compaction[5] "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 somatic cell nuclear transfer (SCNT) embryos was delayed compared with that of intracytoplasmic sperm injection (ICSI) embryos."
More recent papers  
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Zygote Development


<pubmed limit=5>Zygote Development</pubmed>

Movies

Movies

Human fertilization 1 icon.jpg
 ‎‎Fertilisation to
4 Blastomere
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 ‎‎Fertilization
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 ‎‎Fertilization
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Pronuclear fusion 001 icon.jpg
 ‎‎Pronuclear Fusion
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Fertilization 001 icon.jpg
 ‎‎Mouse Fertilisation
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Mouse zygote division icon.jpg
 ‎‎Zygote Mitosis
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 ‎‎Early Division
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Parental genome mix 01 icon.jpg
 ‎‎Parental Genomes
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 ‎‎Mouse Blastocyst
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Human Zygote Size

Actual Size 5cm ruler.jpg

Enlarged Size Stage1 size with ruler.jpg


Parental Pronuclei

  • Maternal pronuclei - (oocyte) genome is inherited from the meiosis II oocyte where the chromosomes are condensed in a mitotic‐like state.
  • Paternal pronuclei - (spermatozoa) genome is contributed by a compacted sperm chromatin that is remodeled upon fertilization. Chiefly by protamine removal and the original nucleosomal chromatin is established. (More? Male Pronucleus Reprogramming)

Parental Genomes

Labeled parental genomes in an early zygote (mouse)

Animation based upon individual images of mouse maternal and paternal genomes.

Mouse zygote pronuclei
Fluorescent image of early mouse zygote pronuclei DIC image of early mouse zygote pronuclei
Fluorescence[6] DIC Optics showing pronuclear bodies[7]

Male Pronucleus Reprogramming

Mouse zygote paternal genome reprogramming[6]

Mouse zygotes male pronucleus contains 5-hydroxymethylcytosine (5hmC) thought to be formed by enzymatic oxidation of 5-methylcytosine (5mC).

  • A - Mouse zygote double-stained with anti-5hmC antibody (green) and anti-5mC antibody (red). The smaller maternal pronucleus is closer to the polar body (pb). A bright-field image is shown on the far left.
  • B - Additional zygotes double-stained with anti-5hmC antibody (green) and anti-5mC antibody (red). Merged images are shown.
  • C - Zygotes obtained by in vitro fertilization were double-stained similarly. Two polyspermic zygotes (to the right) exhibit 5hmC staining in two paternal pronuclei.
  • D - 5mC and 5hmC staining reveal two separate chromosome sets at metaphase of zygote division. A confocal image is shown.
  • E - Individual chromosomes are largely stained for either 5mC (likely originated from the maternal pronucleus) or 5hmC (likely from the paternal pronucleus) at anaphase of zygote division. Two Z sections of the same zygote are shown.


Links: Epigenetics
Mouse zygote paternal genome reprogramming 01.jpg

Mouse zygote mitosis[6]

Mouse zygote mitosis metaphase.jpg Mouse zygote mitosis anaphase.jpg

Subcortical Maternal Complex

The Subcortical Maternal Complex (SCMC) is peripheral cellular region identified in mouse oogenesis, but also present in human, required for determining the first cleavage-stages of division. The SCMA functions in: zygotic genome activation, F-actin dynamics, genome stability, organelle organization, and DNA methylation maintenance at imprinted loci.[8]

Identified Proteins in mouse - Mater, Filia, Floped, Tle6, Zbed3, Nlrp2, possibly Padi6, and other proteins.


Nucleolar-Precursor Bodies

Mouse zygote pronuclei 02.jpg

Most ribosomal DNA located around the Nucleolar-Precursor Bodies (NPBs), with some associated with pericentromeric filaments (extending from the NPBs towards the nuclear periphery) as well as rDNA signals joining two NPBs.[9]

Formation of Zygote

  • male and female pronuclei, 2 nuclei approach each other and nuclear membranes break down
  • DNA replicates, first mitotic division
  • sperm contributes centriole which organizes mitotic spindle

Human zygote two pronuclei 22.jpg Parental genome mix 01 icon.jpg

Movie - Pronuclear Fusion | Movie - Parental Genomes

Conceptus - term refers to all material derived from this fertilized zygote and includes both the embryo and the non-embryonic tissues (placenta, fetal membranes).

Zygote Protein Expression

Maternally inherited Yes-associated protein (Yap), a co-activator of TEAD family transcription factors, plays a key role in activating embryonic transcription following fertilization in the mouse. Lysophosphatidic acid (LPA) in the mouse tubal fluid binds to its G-protein coupled receptor at the plasma membrane, and induces the activation of YAP by inhibiting LATS1/2.[10] Hippo


Mouse- zygote protein expression.jpg

The table above shows the pattern of protein expression (as percentages of total) in the mouse zygote according to 14 molecular function categories.[11]

Links: Germinal vesicle oocyte protein expression | MII oocyte protein expression | Zygote Protein Expression | mouse | oocyte | zygote


References

  1. Ladstätter S & Tachibana-Konwalski K. (2016). A Surveillance Mechanism Ensures Repair of DNA Lesions during Zygotic Reprogramming. Cell , 167, 1774-1787.e13. PMID: 27916276 DOI.
  2. Mackay DJG & Temple IK. (2017). Human imprinting disorders: Principles, practice, problems and progress. Eur J Med Genet , 60, 618-626. PMID: 28818477 DOI.
  3. Niakan KK & Eggan K. (2013). Analysis of human embryos from zygote to blastocyst reveals distinct gene expression patterns relative to the mouse. Dev. Biol. , 375, 54-64. PMID: 23261930 DOI.
  4. Silvestre F, Gallo A, Cuomo A, Covino T & Tosti E. (2011). Role of cyclic AMP in the maturation of Ciona intestinalis oocytes. Zygote , 19, 365-71. PMID: 20810008 DOI.
  5. Li CB, Wang ZD, Zheng Z, Hu LL, Zhong SQ & Lei L. (2011). Number of blastomeres and distribution of microvilli in cloned mouse embryos during compaction. Zygote , 19, 271-6. PMID: 20735894 DOI.
  6. 6.0 6.1 6.2 Iqbal K, Jin SG, Pfeifer GP & Szabó PE. (2011). Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine. Proc. Natl. Acad. Sci. U.S.A. , 108, 3642-7. PMID: 21321204 DOI.
  7. Singer AB & Gall JG. (2011). An inducible nuclear body in the Drosophila germinal vesicle. Nucleus , 2, 403-9. PMID: 21941118 DOI.
  8. Lu X, Gao Z, Qin D & Li L. (2017). A Maternal Functional Module in the Mammalian Oocyte-To-Embryo Transition. Trends Mol Med , 23, 1014-1023. PMID: 28993030 DOI.
  9. Aguirre-Lavin T, Adenot P, Bonnet-Garnier A, Lehmann G, Fleurot R, Boulesteix C, Debey P & Beaujean N. (2012). 3D-FISH analysis of embryonic nuclei in mouse highlights several abrupt changes of nuclear organization during preimplantation development. BMC Dev. Biol. , 12, 30. PMID: 23095683 DOI.
  10. Yu C, Ji SY, Dang YJ, Sha QQ, Yuan YF, Zhou JJ, Yan LY, Qiao J, Tang F & Fan HY. (2016). Oocyte-expressed yes-associated protein is a key activator of the early zygotic genome in mouse. Cell Res. , 26, 275-87. PMID: 26902285 DOI.
  11. Wang S, Kou Z, Jing Z, Zhang Y, Guo X, Dong M, Wilmut I & Gao S. (2010). Proteome of mouse oocytes at different developmental stages. Proc. Natl. Acad. Sci. U.S.A. , 107, 17639-44. PMID: 20876089 DOI.

Journals

  • 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.

Reviews

Lu X, Gao Z, Qin D & Li L. (2017). A Maternal Functional Module in the Mammalian Oocyte-To-Embryo Transition. Trends Mol Med , 23, 1014-1023. PMID: 28993030 DOI.

Jukam D, Shariati SAM & Skotheim JM. (2017). Zygotic Genome Activation in Vertebrates. Dev. Cell , 42, 316-332. PMID: 28829942 DOI.

Destouni A & Vermeesch JR. (2017). How can zygotes segregate entire parental genomes into distinct blastomeres? The zygote metaphase revisited. Bioessays , 39, . PMID: 28247957 DOI.

Chaigne A, Terret ME & Verlhac MH. (2017). Asymmetries and Symmetries in the Mouse Oocyte and Zygote. Results Probl Cell Differ , 61, 285-299. PMID: 28409310 DOI.

Yartseva V & Giraldez AJ. (2015). The Maternal-to-Zygotic Transition During Vertebrate Development: A Model for Reprogramming. Curr. Top. Dev. Biol. , 113, 191-232. PMID: 26358874 DOI.


Articles

Yuan P, Zheng L, Liang H, Li Y, Zhao H, Li R, Lai L, Zhang Q & Wang W. (2018). A novel mutation in the TUBB8 gene is associated with complete cleavage failure in fertilized eggs. J. Assist. Reprod. Genet. , , . PMID: 29704226 DOI.

Conti M & Franciosi F. (2018). Acquisition of oocyte competence to develop as an embryo: integrated nuclear and cytoplasmic events. Hum. Reprod. Update , 24, 245-266. PMID: 29432538 DOI.

Ho JR, Arrach N, Rhodes-Long K, Salem W, McGinnis LK, Chung K, Bendikson KA, Paulson RJ & Ahmady A. (2018). Blastulation timing is associated with differential mitochondrial content in euploid embryos. J. Assist. Reprod. Genet. , , . PMID: 29353449 DOI.

Gassler J, Brandão HB, Imakaev M, Flyamer IM, Ladstätter S, Bickmore WA, Peters JM, Mirny LA & Tachibana K. (2017). A mechanism of cohesin-dependent loop extrusion organizes zygotic genome architecture. EMBO J. , 36, 3600-3618. PMID: 29217590 DOI.


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Cite this page: Hill, M.A. (2018, December 16) Embryology Zygote. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Zygote

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© Dr Mark Hill 2018, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G