Zygote

Embryology - 2 Dec 2023        Expand to Translate
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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 zygote will therefore form the conceptus, the embryonic (embryo, fetus) and extra-embryonic (fetal membranes, fetal component of the placenta) cellular products of fertilisation.

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.

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.

Some Recent Findings

Pleomorphic Adenoma Gene 1 Is Needed For Timely Zygotic Genome Activation and Early Embryo Development "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." Human embryos from zygote to blastocyst reveals distinct gene expression patterns relative to the mouse "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."

More recent papers

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search PubMed: Zygote Development | Zygotic Genome Activation

Older papers

These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table. See also the Discussion Page for other references listed by year and References on this current page. cyclic AMP in the maturation of Ciona intestinalis oocytes "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 "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."

Movies

Movies

‎‎Fertilisation to 4 Blastomere Page | Play	‎‎Fertilization Page | Play	‎‎Fertilization Page | Play	‎‎Pronuclear Fusion Page | Play
‎‎Mouse Fertilisation Page | Play	‎‎Zygote Mitosis Page | Play	‎‎Early Division Page | Play	‎‎Parental Genomes Page | Play	‎‎Mouse Blastocyst Page | Play

Human Zygote Size

Actual Size

Enlarged Size

Parental Pronuclei

Early Human Zygote, with 2 pronuclei

The pronuclei (singular: pronucleus) are the initial male and female nuclei, containing their respective genetic material, that occur in the early zygote. These two haploid nuclei fuse to form the diploid nucleus of the late zygote.

• 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)

Human pronuclei (EM)

Parental Genomes

Labeled parental genomes in an early zygote (mouse)

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

Mouse zygote pronuclei
Fluorescence	DIC Optics showing pronuclear bodies

Male Pronucleus Reprogramming

Mouse zygote paternal genome reprogramming 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 mitosis

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.

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

Nucleolar-Precursor Bodies

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.

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

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).

Zygotic Genome Activation

Zygotic Genome Activation (ZGA) is a slight misnomer, as the zygote has initially low expression which increases to activation occurring at the 4 to 8 cell transition in the human, the early morula stage. In the mouse ZGA occurs earlier during the 2 cell blastomere stage. A recent study in mouse and human has identified Pleomorphic Adenoma Gene 1 (OMIM PLAG1) is a transcription factor that regulates many genes (1,089 genes) involved ribosome biogenesis and protein synthesis. In the adult, PLAG1 is involved in growth and also cancer development. Dux transcription factor is also associated with ZGA and is positively regulated in the mouse by developmental pluripotency-associated 2 (Dppa2) and Dppa4.

Links: GHR PLAG1 | OMIM PLAG1

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. Hippo

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

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

References

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

Eckersley-Maslin M, Alda-Catalinas C, Blotenburg M, Kreibich E, Krueger C & Reik W. (2019). Dppa2 and Dppa4 directly regulate the Dux-driven zygotic transcriptional program. Genes Dev. , 33, 194-208. PMID: 30692203 DOI.

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.

Search Pubmed

June 2010 "zygote" All (6213) Review (651) Free Full Text (1543)

Search Pubmed: zygote

Glossary Links

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Cite this page: Hill, M.A. (2023, December 2) Embryology Zygote. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Zygote

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© Dr Mark Hill 2023, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G