Blastocyst Development

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Human Blastocyst (day 5)[1]

(Greek, blastos = sprout + cystos = cavity) or blastula, the term used to describe the hollow cellular mass that forms in early development. The blastocyst consists of cells forming an outer trophoblast layer, an inner cell mass and a fluid-filled cavity. The blastocyst inner cell mass is the source of true embryonic stem cells capable of forming all cell types within the embryo. In humans, this stage occurs in the first and second weeks after the zygote forms a solid cellular mass morula stage) and before implantation.

Links: Fertilization | Week 1 | Morula | Blastocyst Development | Implantation

Some Recent Findings

  • Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage[2] "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)."
  • Blastocyst gene expression correlates with implantation potential[3] "Compared with blastocysts that resulted in healthy fetal development, blastocysts that failed to implant (negative) showed decreased B3gnt5 and Eomes gene expression, while blastocysts that resulted in spontaneous pregnancy loss (absorption) displayed decreased Wnt3a and Eomes gene expression."
  • FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst[4] "Primitive endoderm (PE) and epiblast (EPI) are two lineages derived from the inner cell mass (ICM) of the E3.5 blastocyst. Recent studies showed that EPI and PE progenitors expressing the lineage-specific transcriptional factors Nanog and Gata6, respectively, arise progressively as the ICM develops. ... In conclusion, we propose a model in which stochastic and progressive specification of EPI and PE lineages occurs during maturation of the blastocyst in an FGF/MAP kinase signal-dependent manner."


Human Blastocyst

 ‎‎Day 3 to 6
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Human blastocyst day 5-6.jpg
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Human blastocyst hatching movie icon.jpg
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Model Development

Model embryo to 32 cell stage icon.jpg
 ‎‎Morula Model
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Model embryo to 128 cell stage icon.jpg
 ‎‎Blastocyst Model
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Human Blastocyst Formation

The table below shows human blastocyst in vitro development changes during week 1.[5]

Human blastocyst formation-in vitro.jpg

Labeled Blastocyst

Human embryo day 5 label.jpg Human embryo day 5 label2.jpg

Blastocyst Hatching

Mouse Blastocyst hatching[6]
Mouse-hatching blastocyst.jpg Human carnegie stage 3 label.jpg
Blastocyst hatching from zona pellucida (mouse) Blastocyst hatching from zona pellucida (human)

Model Human Blastocyst Development

The following figure is from a recent study[2] using video and genetic analysis of in vitro human development during week 1 following fertilization.

Model human blastocyst development.jpg

  • EGA - embryonic genome activation
  • ESSP - embryonic stage–specific pattern, four unique embryonic stage–specific patterns (1-4)
Links: Figure with legend

Mouse Blastocyst Gene Expression

Mouse- preimplantation gene expression.jpg

General gene expression patterns are indicated from genomic profiling.[7]

  • red - loss of maternal mRNAs
  • green - activation of embryonic genome (EGA)
  • purple - maternal gene activation (MGA)
  • orange - continuous expression

Inner Cell Mass

Human Blastocyst (day 5)[1]

This outer layer of cells is also called the "embryoblast", a cluster of cells located and attached on one wall of the outer trophoblast layer.

Trophoblast Layer

This outer layer of cells is also called the "trophectoderm" (TE) epithelium. A key function is for the transport of sodium (Na+) and chloride (Cl-) ions through this layer into the blastocoel.

Differentiation of this layer has been shown to be regulated by the transcription factors Tead4[8] and then Caudal-related homeobox 2 (Cdx2).

Links: Trophoblast | OMIM -Tead4 | OMIM - Cdx2

Blastocoel Formation

Mouse - blastocoel formation[7]
  • trophectoderm transports of Na+ and Cl- ions through this layer into the blastocoel
  • generates an osmotic gradient driving fluid across this epithelium
  • distinct apical and basolateral membrane domains specific for transport
  • facilitates transepithelial Na+ and fluid transport for blastocoel formation
  • transport is driven by Na, K-adenosine triphosphatase (ATPase) in basolateral membranes of the trophectoderm [9]

Blastocyst Metabolism

Mouse blastocyst GLUT8 expression.[10]

At the blastocyst stage, mammalian development metabolism switches on anaerobic glycolysis metabolism to satisfy metabolic demands of growing blastocyst and formation of the blastocoel. This is thought to be driven by the integral membrane protein family of facilitative glucose transporters (GLUT or SLC2A).

  • aerobic - oxidation of lactate and pyruvate via the citric acid cycle (Krebs cycle) and oxidative phosphorylation
  • glycolysis- converts glucose into pyruvate
  • GLUT - GLUcose Transporter (divided into 3 classes I-III)
  • SLC2 - Solute Carrier Family 2

Glucose Transporter Expression

  • GLUT1 - from zygote to blastocyst. (all mammalian tissues, basal glucose uptake)
  • GLUT2 and GLUT3 - from late eight cell stage to blastocyst. (GLUT2, liver and pancreatic beta cells; GLUT3, all mammalian tissues, basal glucose uptake)
  • GLUT4 - not expressed. (muscle and adipose tissue)
  • GLUT8 - up-regulated at blastocyst stage. (central nervous system and heart)
(Data mainly from mouse development, adult tissue expression shown in brackets)

A mouse study,[10] has shown GLUT8 is up-regulated following insulin stimulation, though a more recent GLUT8 knockout mouse shows normal early embryonic development in the absence of this transporter.[11]

Links: Biochemistry - glucose transporters | GLUT1 | GLUT2 | GLUT8

Blastula Cell Communication

Two types of cell junctions have been identified located at different regions in the developing blastocyst.

Tight junctions

Located close to outer surface create a seal, isolates interior of embryo from external medium.

Gap junctions

Allow electrically coupling of the cells of epithelium surrounding the fluid-filled cavity.

Tight junction 01.jpg Gap junction 01.jpg
Adhesion EM Images: GIT epithelia EM1 | GIT epithelia EM2 | GIT epithelia EM3 | Desmosome EM
Adhesion Cartoons: Tight junction | Adherens Junction | Desmosome | Gap Junction

Blastocyst Hatching - zona pellucida lost, ZP has sperm entry site, and entire ZP broken down by uterine secretions and possibly blastula secretions.

Uterine Glands - secretions required for blastocyst motility and nutrition

Links: MBoC Figure 21-69. The blastula

Blastocyst Hatching

At about day 5 the human blastocyst "hatches" out of the protective zona pellucida. This hatching allows increased growth, access to uterine nutrient secretions and blastocyst adhesion to the uterine lining. Associated with this hatching process are a series of physical contractions.

In the blastocyst, repeated contractions occur after blastocoel formation and the frequency of contractions is greater during the hatching period than in the periods both before and after hatching.[12] Interestingly, the same researchers in this mouse study suggest that the weaker contractions (less than 20% volume reduction) seen have a role in hatching, in contrast to strong contractions (20% or more volume reduction) have the opposite effect of inhibiting hatching.

In the mouse model, the identified sites of zona pellucida shedding varied (24% mural site, 24% inner cell mass site, 17% equatorial site, and 35% other sites).[13]

Links: Blastocyst Day 5-6 Movie
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Human blastocyst contractions (day 5-6)[2]

Molecular Factors

  • TEA DNA- binding domain, these factors bind to the consensus TEA/ATTS cognate binding site[14]
    • TEF-3 - renamed Tead1 and Tead4
    • Tead3 - is expressed in the placental syncytiotrophoblasts
  • E-cadherin - Calcium ion-dependent cell adhesion molecule, a cell membrane adhesive protein required for morula compaction
  • epithin - A type II transmembrane serine protease, identified in mouse for compaction of the morula during preimplantation embryonic development. Expressed from 8-cell stage at blastomere contacts and co-localises in the morula with E-cadherin. PMID: 15848395
  • Na, K-adenosine triphosphatase - A sodium potassium pump that generates an osmotic gradient for fluid flow into the blastocoel
  • Zonula occludens-1 - (ZO-1) Tight junction protein involved in morula to blastocyst transformation in the mouse PMID: 18423437

Blastocyst in Other Species

Mouse Blastocyst

Early mouse development cartoon.jpg

Early mouse development model[16]

Links: Mouse Development

Bovine Blastocyst

Links: Bovine Development


  1. 1.0 1.1 Pu Zhang, Marco Zucchelli, Sara Bruce, Fredwell Hambiliki, Anneli Stavreus-Evers, Lev Levkov, Heli Skottman, Erja Kerkelä, Juha Kere, Outi Hovatta Transcriptome profiling of human pre-implantation development. PLoS ONE: 2009, 4(11);e7844 PMID: 19924284 | PMC2773928 | PLoS One
  2. 2.0 2.1 2.2 Connie C Wong, Kevin E Loewke, Nancy L Bossert, Barry Behr, Christopher J De Jonge, Thomas M Baer, Renee A Reijo Pera Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage. Nat. Biotechnol.: 2010, 28(10);1115-21 PMID: 20890283 | Nat Biotechnol.
  3. Jason C Parks, Blair R McCallie, Ann M Janesch, William B Schoolcraft, Mandy G Katz-Jaffe Blastocyst gene expression correlates with implantation potential. Fertil. Steril.: 2011, 95(4);1367-72 PMID: 20864103
  4. Yojiro Yamanaka, Fredrik Lanner, Janet Rossant FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst. Development: 2010, 137(5);715-24 PMID: 20147376
  5. C Y Fong, A Bongso Comparison of human blastulation rates and total cell number in sequential culture media with and without co-culture. Hum. Reprod.: 1999, 14(3);774-81 PMID: 10221713
  6. Noriko Tanaka, Takumi Takeuchi, Queenie V Neri, Eric Scott Sills, Gianpiero D Palermo Laser-assisted blastocyst dissection and subsequent cultivation of embryonic stem cells in a serum/cell free culture system: applications and preliminary results in a murine model. J Transl Med: 2006, 4;20 PMID: 16681851 | PMC1479373 | J Transl Med.
  7. 7.0 7.1 Christine E Bell, Michele D Calder, Andrew J Watson Genomic RNA profiling and the programme controlling preimplantation mammalian development. Mol. Hum. Reprod.: 2008, 14(12);691-701 PMID: 19043080 | Mol Hum Reprod.
  8. Noriyuki Nishioka, Shinji Yamamoto, Hiroshi Kiyonari, Hiroko Sato, Atsushi Sawada, Mitsunori Ota, Kazuki Nakao, Hiroshi Sasaki Tead4 is required for specification of trophectoderm in pre-implantation mouse embryos. Mech. Dev.: 2007, 125(3-4);270-83 PMID: 18083014
  9. Gerald M Kidder, Andrew J Watson Roles of Na,K-ATPase in early development and trophectoderm differentiation. Semin. Nephrol.: 2005, 25(5);352-5 PMID: 16139691
  10. 10.0 10.1 M O Carayannopoulos, M M Chi, Y Cui, J M Pingsterhaus, R A McKnight, M Mueckler, S U Devaskar, K H Moley GLUT8 is a glucose transporter responsible for insulin-stimulated glucose uptake in the blastocyst. Proc. Natl. Acad. Sci. U.S.A.: 2000, 97(13);7313-8 PMID: 10860996 | PMC16542 | Proc Natl Acad Sci U S A.
  11. Mathieu Membrez, Edith Hummler, Friedrich Beermann, Jacques-Antoine Haefliger, Rebecca Savioz, Thierry Pedrazzini, Bernard Thorens GLUT8 is dispensable for embryonic development but influences hippocampal neurogenesis and heart function. Mol. Cell. Biol.: 2006, 26(11);4268-76 PMID: 16705176
  12. Sueo Niimura Time-lapse videomicrographic analyses of contractions in mouse blastocysts. J. Reprod. Dev.: 2003, 49(6);413-23 PMID: 14967891
  13. K Yamazaki, Y Kato Sites of zona pellucida shedding by mouse embryo other than muran trophectoderm. J. Exp. Zool.: 1989, 249(3);347-9 PMID: 2708952
  14. P Jacquemin, J J Hwang, J A Martial, P Dollé, I Davidson A novel family of developmentally regulated mammalian transcription factors containing the TEA/ATTS DNA binding domain. J. Biol. Chem.: 1996, 271(36);21775-85 PMID: 8702974
  15. 15.0 15.1 15.2 15.3 15.4 Maria Keramari, Janet Razavi, Karen A Ingman, Christoph Patsch, Frank Edenhofer, Christopher M Ward, Susan J Kimber Sox2 is essential for formation of trophectoderm in the preimplantation embryo. PLoS ONE: 2010, 5(11);e13952 PMID: 21103067 | PMC2980489 | PLoS One.
  16. Pawel Krupinski, Vijay Chickarmane, Carsten Peterson Simulating the mammalian blastocyst--molecular and mechanical interactions pattern the embryo. PLoS Comput. Biol.: 2011, 7(5);e1001128 PMID: 21573197 | PMC3088645 | PLoS Comput Biol.


Theodore P Rasmussen, Gareth N Corry Epigenetic pre-patterning and dynamics during initial stages of mammalian preimplantation development. J. Cell. Physiol.: 2010, 225(2);333-6 PMID: 20607796

Katie Cockburn, Janet Rossant Making the blastocyst: lessons from the mouse. J. Clin. Invest.: 2010, 120(4);995-1003 PMID: 20364097

Janet Rossant Stem cells and lineage development in the mammalian blastocyst. Reprod. Fertil. Dev.: 2007, 19(1);111-8 PMID: 17389140


Joana Santos, C Filipe Pereira, Aida Di-Gregorio, Thomas Spruce, Olivia Alder, Tristan Rodriguez, Véronique Azuara, Matthias Merkenschlager, Amanda G Fisher 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: 2010, 3;1 PMID: 20157423

Bette J Dzamba, Karoly R Jakab, Mungo Marsden, Martin A Schwartz, Douglas W DeSimone Cadherin adhesion, tissue tension, and noncanonical Wnt signaling regulate fibronectin matrix organization. Dev. Cell: 2009, 16(3);421-32 PMID: 19289087

Bhavwanti Sheth, Rachael L Nowak, Rebecca Anderson, Wing Yee Kwong, Thomas Papenbrock, Tom P Fleming Tight junction protein ZO-2 expression and relative function of ZO-1 and ZO-2 during mouse blastocyst formation. Exp. Cell Res.: 2008, 314(18);3356-68 PMID: 18817772

Noriyuki Nishioka, Shinji Yamamoto, Hiroshi Kiyonari, Hiroko Sato, Atsushi Sawada, Mitsunori Ota, Kazuki Nakao, Hiroshi Sasaki Tead4 is required for specification of trophectoderm in pre-implantation mouse embryos. Mech. Dev.: 2007, 125(3-4);270-83 PMID: 18083014

Yojiro Yamanaka, Amy Ralston, Robert O Stephenson, Janet Rossant Cell and molecular regulation of the mouse blastocyst. Dev. Dyn.: 2006, 235(9);2301-14 PMID: 16773657 | Dev. Dyn.

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Cite this page: Hill, M.A. (2014) Embryology Blastocyst Development. Retrieved January 30, 2015, from

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