Blastocyst Development

From Embryology

Introduction

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."

Recent References | References

Movies

Human Blastocyst

Human-blastocyst-day-3-6-icon.jpg
 ‎‎Day 3 to 6
Page | Play
Human blastocyst day 5-6.jpg
 ‎‎Contractions
Page | Play
Human blastocyst hatching movie icon.jpg
 ‎‎Hatching
Page | Play

Model Development

Model embryo to 32 cell stage icon.jpg
 ‎‎Morula Model
Page | Play
Model embryo to 128 cell stage icon.jpg
 ‎‎Blastocyst Model
Page | Play

Movies

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)

Blastocyst Movies

The following movies are from two recent papers. The first looking at live in vitro human blastocyst development (day 3-6).[2] The second is a simulation of mouse blastocyst development using known differential adhesion and directional signal mechanisms. [7]

Select the Quicktime or Flash format to view annotated movies.

Human-blastocyst-day-3-6-icon.jpg Human blastocyst day 5-6.jpg Human blastocyst hatching movie icon.jpg Model embryo to 128 cell stage icon.jpg
Blastocyst Development

Quicktime | Flash

Blastocyst Contractions

Quicktime | Flash

Blastocyst Hatching

Quicktime | Flash

Blastocyst Simulation

Quicktime | Flash

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.[8]

  • 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[9] and then Caudal-related homeobox 2 (Cdx2).


Links: Trophoblast | OMIM -Tead4 | OMIM - Cdx2

Blastocoel Formation

Mouse - blastocoel formation[8]
  • 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 [10]

Blastocyst Metabolism

Mouse blastocyst GLUT8 expression.[11]

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,[11] 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.[12]

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.[13] 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).[14]

Links: Quicktime - Blastocyst Contractions | Flash - Blastocyst Contractions | Quicktime - Blastocyst Hatching | Flash - Blastocyst Hatching
width=250px|height=240px|controller=true|autoplay=false</qt>

Human blastocyst contractions (day 5-6)[2]

Quicktime | Flash

Molecular Factors

  • TEA DNA- binding domain, these factors bind to the consensus TEA/ATTS cognate binding site[15]
    • 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[17]

Bovine Blastocyst

References

  1. 1.0 1.1 <pubmed>19924284</pubmed>| PMC2773928 | PLoS One
  2. 2.0 2.1 2.2 2.3 <pubmed>20890283</pubmed>| Nat Biotechnol.
  3. <pubmed>20864103</pubmed>
  4. <pubmed>20147376</pubmed>
  5. <pubmed>10221713</pubmed>
  6. <pubmed>16681851</pubmed>| PMC1479373 | J Transl Med.
  7. 21573197</pubmed>| PMC3088645 | PLoS Comput Biol.
  8. 8.0 8.1 <pubmed>19043080</pubmed>| Mol Hum Reprod.
  9. <pubmed>18083014</pubmed>
  10. <pubmed>16139691</pubmed>
  11. 11.0 11.1 <pubmed>10860996</pubmed>| PMC16542 | Proc Natl Acad Sci U S A.
  12. <pubmed>16705176</pubmed>
  13. <pubmed>14967891</pubmed>
  14. <pubmed>2708952 </pubmed>
  15. <pubmed>8702974</pubmed>
  16. 16.0 16.1 16.2 16.3 16.4 <pubmed>21103067</pubmed>| PMC2980489 | PLoS One.
  17. <pubmed>21573197</pubmed>| PMC3088645 | PLoS Comput Biol.


Reviews

<pubmed>20607796</pubmed> <pubmed>20364097</pubmed> <pubmed>17389140</pubmed>

Articles

<pubmed>20157423</pubmed> <pubmed>19289087</pubmed> <pubmed>18817772</pubmed> <pubmed>18083014</pubmed> <pubmed>16773657</pubmed>| Dev. Dyn.

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Search Pubmed: blastocyst development | blastocoel development | inner cell mass development | trophectoderm |


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Cite this page: Hill, M.A. (2024, March 19) Embryology Blastocyst Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Blastocyst_Development

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G