Morula Development

Embryology - 5 Dec 2023 Expand to Translate
Google Translate - select your language from the list shown below (this will open a new external page)
العربية \| català \| 中文 \| 中國傳統的 \| français \| Deutsche \| עִברִית \| हिंदी \| bahasa Indonesia \| italiano \| 日本語 \| 한국어 \| မြန်မာ \| Pilipino \| Polskie \| português \| ਪੰਜਾਬੀ ਦੇ \| Română \| русский \| Español \| Swahili \| Svensk \| ไทย \| Türkçe \| اردو \| ייִדיש \| Tiếng Việt These external translations are automated and may not be accurate. (More? About Translations)

Introduction

Human morula (day 2)^[1]

Human morula (day 3)^[1]

(Latin, morula = mulberry) An early stage in post-fertilization development when cells have rapidly mitotically divided to produce a solid mass of cells (12-15 cells) with a "mulberry" appearance. This stage is followed by formation of a cavity in this cellular mass blastocyst stage.

A key event prior to morula formation is "compaction", where the 8 cell embryo undergoes changes in cell morphology and cell-cell adhesion that initiates the formation of this solid ball of cells.

In humans, morula stage of development occurs during the first days in week one following fertilization (GA week 3) and is described as Carnegie stage 2. This stage is followed by formation of a cavity, the blastocoel, which defines formation of the blastocyst.

ART Preimplantation blastomere biopsy^[2]

In Assisted Reproductive Technology, the morula stage is when one of the earliest prenatal diagnostic test can be carried out, by removing a single cell (blastomere) and carrying out genetic diagnosis on its DNA.

Molecular - In the mouse, during transition from morula to blastocyst stage, differentiation of the inner cell mass (ICM) and trophectoderm (TE) has been shown to be regulated by the Hippo pathway.^[3]^[4]

Some Recent Findings

Effect of Downregulating the Hippo Pathway Members YAP1 and LATS2 Transcripts on Early Development and Gene Expression Involved in Differentiation in Porcine Embryos^[4] "In mouse development, differentiation of the inner cell mass (ICM) and trophectoderm (TE) during the transition from the morula to blastocyst stage is regulated by the Hippo pathway; however, the functions of the Hippo pathway in porcine embryogenesis have not been investigated. In the present study, we examined the gene expression patterns of the Hippo pathway members yes-associated protein 1 (YAP1) and large tumor suppressor 2 (LATS2) and the functions of these genes during porcine preimplantation development using RNA interference. Both YAP1 and LATS2 mRNA levels were shown high in the in vitro matured oocytes and 1-cell stage embryos and fell progressively with development. YAP1 nuclear localization was detected at the morula and blastocyst stages. Downregulation of either YAP1 or LATS2 inhibited porcine preimplantation development and affected the expression levels of POU class 5 homeobox 1 (OCT-4) and SRY-related HMG-box gene 2 (SOX2), transcription factors necessary for the ICM/TE differentiation. Taken together, YAP1 and LATS2 are essential for porcine preimplantation development, and it is possible that the Hippo pathway has important roles in porcine ICM/TE segregation."

Diversity of human and mouse homeobox gene expression in development and adult tissues^[5] "8-cell to morula, 12 eutherian-specific homeobox genes not detectable outside of reproductive tissues or the embryo (RHOXF2, RHOXF2B, CPHX1, CPHX2, DPRX, LEUTX, TPRX1, TPRX2, ARGFX, NANOGNB, DUXA, DUXB). Hox

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 term: Morula Development \| Morula Compaction \| Morula Blastomere Division \| Morula Hippo \|

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. Par-aPKC-dependent and -independent mechanisms cooperatively control cell polarity, Hippo signaling, and cell positioning in 16-cell stage mouse embryos^[3] "In preimplantation mouse embryos, the Hippo signaling pathway plays a central role in regulating the fates of the trophectoderm (TE) and the inner cell mass (ICM). In early blastocysts with more than 32 cells, the Par-aPKC system controls polarization of the outer cells along the apicobasal axis, and cell polarity suppresses Hippo signaling." Hippo \| mouse Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage^[6] "We report studies of preimplantation human embryo development that correlate time-lapse image analysis and gene expression profiling. By examining a large set of zygotes from in vitro fertilization (IVF), we find that success in progression to the blastocyst stage can be predicted with >93% sensitivity and specificity by measuring three dynamic, noninvasive imaging parameters by day 2 after fertilization, before embryonic genome activation (EGA)." Functional genomics of 5- to 8-cell stage human embryos by blastomere single-cell cDNA analysis^[7] "Forty-nine blastomeres from 5- to 8-cell human embryos have been investigated following an efficient single-cell cDNA amplification protocol to provide a template for high-density microarray analysis. The previously described markers, characteristic of Inner Cell Mass (ICM) (n = 120), stemness (n = 190) and Trophectoderm (TE) (n = 45), were analyzed, and a housekeeping pattern of 46 genes was established. ...In summary, the global single-cell cDNA amplification microarray analysis of the 5- to 8-cell stage human embryos reveals that blastomere fate is not committed to ICM or TE."

Movies

‎‎Morula Model

Page | Play

‎‎Zygote Mitosis

Page | Play

‎‎Early Division

Page | Play

‎‎Parental Genomes

Page | Play

‎‎Mouse Blastocyst

Page | Play

Movies

Compaction

E-cadherin mediated adhesion initiates at compaction at the 8-cell stage
regulated post-translationally via protein kinase C and other signalling molecules

Blastomere Division

Spindle orientation calculation.^[8]

An in vitro study of human blastocyst development^[9] showed that those blastomeres that initially divide quickly are more likely to develop to blastocyst stage.

A recent study in mice showed that there was no specific orientation of the mitotic spindle during cell division in the 8 to 16 cell stage transition.^[8] This suggests no predetermined cleavage pattern (pre-patterned) at the 8 cell stage and only modulated by the extent of cell rounding up during mitosis. In other species, such as the worm C.elegans and ascidians, have specific patterns of spindle orientation from the zygote stage.

Model Human Morula Development

The following figure is from a recent study^[6] using video and genetic analysis of in vitro human development during week 1 following fertilization.

EGA - embryonic genome activation
ESSP - embryonic stage–specific pattern, four unique embryonic stage–specific patterns (1-4)

Links: Figure with legend

Morulas in Other Species

Mouse Morula

In the mouse, during transition from morula to blastocyst stage, differentiation of the inner cell mass (ICM) and trophectoderm (TE) has been shown to be regulated by the Hippo pathway.^[4]

4 cell morula stage development
Sox2 expression
Early gene expression
Early gene expression
Early gene expression
Early gene expression

Links: Mouse Development

Sea Urchin Morula

Sea Urchin early embryo cleavage pattern (SDB Gallery Images)

Links: Sea Urchin Development

Bovine Morula

Bovine Morula^[10]

Image shows DNA staining (white) and f-actin filaments (orange) at day 4. Scale bars represent 100 µm.
Pale staining round nuclei are at interphase.
Arrow shows single nucleus at prophase.
A single nucleus is seen at metaphase.
Condensed bright nuclei are apoptotic.

Links: Bovine Development | mitosis

Morula Biopsy

Biopsy of compact morula-stage embryos^[11]

(A) A compact morula-stage embryo before biopsy.
(B–G) Steps of the biopsy.
(H) An embryo at 2 h after biopsy.

Links: Prenatal Diagnosis | Assisted Reproductive Technology

References

↑ ^1.0 ^1.1 Zhang P, Zucchelli M, Bruce S, Hambiliki F, Stavreus-Evers A, Levkov L, Skottman H, Kerkelä E, Kere J & Hovatta O. (2009). Transcriptome profiling of human pre-implantation development. PLoS ONE , 4, e7844. PMID: 19924284 DOI.
↑ Milachich T. (2014). New advances of preimplantation and prenatal genetic screening and noninvasive testing as a potential predictor of health status of babies. Biomed Res Int , 2014, 306505. PMID: 24783200 DOI.
↑ ^3.0 ^3.1 Hirate Y, Hirahara S, Inoue K, Kiyonari H, Niwa H & Sasaki H. (2015). Par-aPKC-dependent and -independent mechanisms cooperatively control cell polarity, Hippo signaling, and cell positioning in 16-cell stage mouse embryos. Dev. Growth Differ. , 57, 544-56. PMID: 26450797 DOI.
↑ ^4.0 ^4.1 ^4.2 Emura N, Saito Y, Miura R & Sawai K. (2020). Effect of Downregulating the Hippo Pathway Members YAP1 and LATS2 Transcripts on Early Development and Gene Expression Involved in Differentiation in Porcine Embryos. Cell Reprogram , , . PMID: 32150685 DOI.
↑ Dunwell TL & Holland PW. (2016). Diversity of human and mouse homeobox gene expression in development and adult tissues. BMC Dev. Biol. , 16, 40. PMID: 27809766 DOI.
↑ ^6.0 ^6.1 Wong CC, Loewke KE, Bossert NL, Behr B, De Jonge CJ, Baer TM & Reijo Pera RA. (2010). Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage. Nat. Biotechnol. , 28, 1115-21. PMID: 20890283 DOI.
↑ Galán A, Montaner D, Póo ME, Valbuena D, Ruiz V, Aguilar C, Dopazo J & Simón C. (2010). Functional genomics of 5- to 8-cell stage human embryos by blastomere single-cell cDNA analysis. PLoS ONE , 5, e13615. PMID: 21049019 DOI.
↑ ^8.0 ^8.1 Dard N, Louvet-Vallée S & Maro B. (2009). Orientation of mitotic spindles during the 8- to 16-cell stage transition in mouse embryos. PLoS ONE , 4, e8171. PMID: 19997595 DOI.
↑ Fenwick J, Platteau P, Murdoch AP & Herbert M. (2002). Time from insemination to first cleavage predicts developmental competence of human preimplantation embryos in vitro. Hum. Reprod. , 17, 407-12. PMID: 11821286
↑ Leidenfrost S, Boelhauve M, Reichenbach M, Güngör T, Reichenbach HD, Sinowatz F, Wolf E & Habermann FA. (2011). Cell arrest and cell death in mammalian preimplantation development: lessons from the bovine model. PLoS ONE , 6, e22121. PMID: 21811561 DOI.
↑ Zakharova EE, Zaletova VV & Krivokharchenko AS. (2014). Biopsy of human morula-stage embryos: outcome of 215 IVF/ICSI cycles with PGS. PLoS ONE , 9, e106433. PMID: 25191937 DOI.

Reviewss

Coticchio G, Lagalla C, Sturmey R, Pennetta F & Borini A. (2019). The enigmatic morula: mechanisms of development, cell fate determination, self-correction and implications for ART. Hum. Reprod. Update , 25, 422-438. PMID: 30855681 DOI.

Articles

Bessonnard S, Mesnard D & Constam DB. (2015). PC7 and the related proteases Furin and Pace4 regulate E-cadherin function during blastocyst formation. J. Cell Biol. , 210, 1185-97. PMID: 26416966 DOI.

Dzamba BJ, Jakab KR, Marsden M, Schwartz MA & DeSimone DW. (2009). Cadherin adhesion, tissue tension, and noncanonical Wnt signaling regulate fibronectin matrix organization. Dev. Cell , 16, 421-32. PMID: 19289087 DOI.

Santos J, Pereira CF, Di-Gregorio A, Spruce T, Alder O, Rodriguez T, Azuara V, Merkenschlager M & Fisher AG. (2010). Differences in the epigenetic and reprogramming properties of pluripotent and extra-embryonic stem cells implicate chromatin remodelling as an important early event in the developing mouse embryo. Epigenetics Chromatin , 3, 1. PMID: 20157423 DOI.

Search PubMed

Search Pubmed: morula development | blastomere development |

Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link

Cite this page: Hill, M.A. (2023, December 5) Embryology Morula Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Morula_Development

What Links Here?

[PMID19924284-1] 1.0 ^1.1 Zhang P, Zucchelli M, Bruce S, Hambiliki F, Stavreus-Evers A, Levkov L, Skottman H, Kerkelä E, Kere J & Hovatta O. (2009). Transcriptome profiling of human pre-implantation development. PLoS ONE , 4, e7844. PMID: 19924284 DOI.

[PMID24783200-2] Milachich T. (2014). New advances of preimplantation and prenatal genetic screening and noninvasive testing as a potential predictor of health status of babies. Biomed Res Int , 2014, 306505. PMID: 24783200 DOI.

[PMID26450797-3] 3.0 ^3.1 Hirate Y, Hirahara S, Inoue K, Kiyonari H, Niwa H & Sasaki H. (2015). Par-aPKC-dependent and -independent mechanisms cooperatively control cell polarity, Hippo signaling, and cell positioning in 16-cell stage mouse embryos. Dev. Growth Differ. , 57, 544-56. PMID: 26450797 DOI.

[PMID32150685-4] 4.0 ^4.1 ^4.2 Emura N, Saito Y, Miura R & Sawai K. (2020). Effect of Downregulating the Hippo Pathway Members YAP1 and LATS2 Transcripts on Early Development and Gene Expression Involved in Differentiation in Porcine Embryos. Cell Reprogram , , . PMID: 32150685 DOI.

[PMID27809766-5] Dunwell TL & Holland PW. (2016). Diversity of human and mouse homeobox gene expression in development and adult tissues. BMC Dev. Biol. , 16, 40. PMID: 27809766 DOI.

[PMID20890283-6] 6.0 ^6.1 Wong CC, Loewke KE, Bossert NL, Behr B, De Jonge CJ, Baer TM & Reijo Pera RA. (2010). Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage. Nat. Biotechnol. , 28, 1115-21. PMID: 20890283 DOI.

[PMID21049019-7] Galán A, Montaner D, Póo ME, Valbuena D, Ruiz V, Aguilar C, Dopazo J & Simón C. (2010). Functional genomics of 5- to 8-cell stage human embryos by blastomere single-cell cDNA analysis. PLoS ONE , 5, e13615. PMID: 21049019 DOI.

[PMID19997595-8] 8.0 ^8.1 Dard N, Louvet-Vallée S & Maro B. (2009). Orientation of mitotic spindles during the 8- to 16-cell stage transition in mouse embryos. PLoS ONE , 4, e8171. PMID: 19997595 DOI.

[PMID11821286-9] Fenwick J, Platteau P, Murdoch AP & Herbert M. (2002). Time from insemination to first cleavage predicts developmental competence of human preimplantation embryos in vitro. Hum. Reprod. , 17, 407-12. PMID: 11821286

[PMID21811561-10] Leidenfrost S, Boelhauve M, Reichenbach M, Güngör T, Reichenbach HD, Sinowatz F, Wolf E & Habermann FA. (2011). Cell arrest and cell death in mammalian preimplantation development: lessons from the bovine model. PLoS ONE , 6, e22121. PMID: 21811561 DOI.

[PMID25191937-11] Zakharova EE, Zaletova VV & Krivokharchenko AS. (2014). Biopsy of human morula-stage embryos: outcome of 215 IVF/ICSI cycles with PGS. PLoS ONE , 9, e106433. PMID: 25191937 DOI.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]