UNSW Embryology

Week 2

© Dr Mark Hill (2011)

Acknowledgements

Introduction

The second week of development is marked by blastocyst development and the implantation process. The cavity within the blastocyst and the inner cell mass that will eventually form the embryo begin early differentiation. The outer trophoblast layer grows rapidly and differentiates to form extraembryonic tissue of the placenta. This section of notes covers individual aspects of these developmental processes (More? Week 2 Overview) as well as introducing the topic of embryonic stem cells (More? Stem Cells). Implantation continues through the following week 3, when the embryo germ layers begins to develop and placental villi will form (More? Week 3 Notes).

Blastocyst (right) hatching from zona pellucida (left) (More? Carnegie Stage 3).

Page Links: Introduction | Some Recent Findings | Reading | Objectives | Computer Activities | Development Overview | Quick Links | References | Glossary

Related Pages: Timeline Week 2 | Carnegie Stage 5 - 7 | Blastocyst Implantation | Sites of Implantation | Bilaminar Embryo | Embryonic Cavities | Early Placentation | Ovary| Twinning | Abnormalities | K12 Week 2 | Molecular | Week 2 Movies | Stem Cells | References | Text only | WWW Links | Abnormalities | K12 Week 2

Some Recent Findings

	Recent findings in mouse have shown that maternal leukemia inhibitory factor (LIF) and p53 has an important role in the implantation process. (More Week 2 - Molecular)
	Implantation Review Makrigiannakis A, Minas V. Mechanisms of implantation. Reprod Biomed Online. 2007 Jan;14(1):102-9.

Blastocyst differentiation Inner cell mass and not trophoblast shell is dependent upon Sall4 (Sal-like genes encode putative zinc finger transcription factors) Elling U, Klasen C, Eisenberger T, Anlag K, Treier M. Murine inner cell mass-derived lineages depend on Sall4 function. Proc Natl Acad Sci U S A. 2006 Oct 23

"Sall4 is cell-autonomously required for the development of the epiblast and primitive endoderm from the inner cell mass. Furthermore, no embryonic or extraembryonic endoderm stem cell lines could be established from Sall4-deficient blastocysts. In contrast, neither the development of the trophoblast lineage nor the ability to generate trophoblast cell lines from murine blastocysts was impaired in the absence of Sall4."

(More? Week 2 - Molecular)

Reading

• Human Embryology (2nd ed.) Larson Chapter 1 p1-32
• The Developing Human: Clinically Oriented Embryology (8th ed.) Moore and Persaud, Chapter 3 pp42-53
• Before we Are Born (5th ed.) Moore and Persaud Chapter 4 pp47-61
• Essentials of Human Embryology Larson Chapter 1 p1-16
• Human Embryology Fitzgerald and Fitzgerald
• UNSW Embryology Selected Week 2 References

Objectives

• Understand the process of blastocyst adplantation/implantation
• Identify the different sites of implantation
• Describe the formation of the embryonic cavities
• Describe the early processes in placentation
• Understand the abnormalities that occur during this period of development

Computer Activities

UNSW Embryology: Introduction | Timeline Week 2 | Carnegie stages 5 to 7 | Abnormalities | Blastocyst Implantation | Sites of Implantation | Bilaminar Embryo | Embryonic Cavitites | Early Placentation | Molecular | Stem Cells | References | Text only | WWW Links | Movies - Week 2

Embryo Images Unit: Unit: Early cell Populations

Embryology Movies: Implantation (451Kb) | Chorionic Cavity (1.2Mb) | Exocoelomic Vesicle (536Kb)

Video: BBC series The Human Body, Episode 2 available commercially as a book by Anthony Smith, video, or CD Rom , short sample video available from ABC (needs realvideo)

Development Overview - Week 2 - Implantation and Gastrulation

• Covering Week 2 of development
  • Finish formation of the Blastocyst
  • trophoblast, embryoblast
• Implantation
  • normal, ectopic
• Changes in the Uterus
  • Early utero-placental circulation
• Formation of
  • the Bilaminar Embryo
  • the 3 chambered conceptus
  • the Trilaminar Embryo
  • the Axial Process
• Early cell division
  • Cleavage of the Zygote
  • cleavage of zygote forms 2 blastomeres
  • cleavage with no cytoplasm synthesis
  • therefore individual cell volume decreases
  • initially synchronously, then asynchronously
• Formation of the Morula
  • there are now 16-20 cells
  • at the end of the oviduct
  • ball of cells
  • slow- centre cells, larger
  • fast- peripheral cells, flattened against zona pellucida
• Formation of the Blastocyst
  • Day 5
  • zona pellucida lost
  • uterine secretions
    • breakdown ZP
    • support blastocyst (nutrition)
  • compaction
    • central cells now compacte
    • located on a region of the wall
  • blastoceol formation
    • cavity formed by compaction
    • fluid filled blastoceol
• Blastocyst
  • Trophoblast
    • forms the placenta
    • placental membranes
  • Embryoblast
    • Inner cell mass
    • forms entire embryo
• Early cell division
• Implantation- Trophoblasts
  • Occurs at day 6-7
  • adhesion
  • adplantation
  • implantation complete by about day 9
• Normal
  • uterine wall
  • posterior, lateral
  • cervix, superior
• Abnormal
  • Tubal or Ectopic- not in uterus
• Abnormal Implantation
  • often occurs if zona pellucida is lost too early allowing premature implantion
  • Tubal pregnancy 94%
  • embryo may develop through early stages.
  • can erode through the uterine horn
  • reattach within the peritoneal cavity
• Ectopic Pregnancy
  • external surface of uterus
  • bowel
  • gastrointestinal tract, mesentry
  • peritoneal wall
  • If not spontaneous then, embryo has to be removed surgically
• Normal Implantation- Endometrium
  • consists of 3 layers in secretatory phase of menstral cycle
    • compact
      • implantation odccurs in this layer
      • dense stromal cells, uterine gland necks, capillaries of spiral arteries
    • spongy
      • swollen stromal cells, uterine gland bodies, spiral arteries
    • basal
      • not lost during menstruation or childbirth, own blood supply
  • Myometrium
    • muscular layer outside endometrium
    • contracts in parturition
• Uterine Changes
  • Endometrium
    • decidual reaction
    • change that occurs in the endometrium at site of implantation
      • loss of epithelium
      • deposition of glycogen
    • spreads throughout uterus
    • not at cervix
    • decidual cells indicative of pregnancy (curette)
    • following reaction endometrium called Decidua
  • Cervix
    • at mouth of uterus
    • secretes mucus
    • forms a plug
  • Vascular
    • increased number of blood vessels
• Decidua
  • forms 3 distinct regions (3 weeks)
    • Decidua Basalis- implantation site
    • Decidua Capsularis- enclosing the conceptus
    • Decidua Parietalis- remainder of uterus
  • Decidua Capsularis and Parietalis fuse- uterine cavity is lost by 12 weeks
• Normal Implantation- Attachment / Adplantation
  • trophoblast cells adhere to uterine endometrium
  • Perlecan, HSPG
  • uterine endometrium expresses binding proteins
  • orients with inner cell mass closest to uterine wall
  • trophoblasts proliferate on attached side
  • uterine LIF required for implantation
  • autocrine / paracrine function
  • proliferating cells loose cell membranes forming syncitiotrophoblasts
  • remainder of trophoblasts- cytotrophoblasts
• Implantation- Day 7
• Implantation- Syncitiotrophoblasts
  • Secrete proteolytic enzymes
  • enzymes break down extracellular matrix around cells
  • Allow passage of Blastocyst into endometrial wall
  • totally surround the blastocyst
  • secrete human chorionic gonadotropin (hCG)
  • presence in urine pregnancy diagnostic
  • maitains decidua and Corpus Luteum
  • generate spaces that fill with maternal blood- lacunae
• coagulation plug
  • left where the blastocyst has entered the uterine wall (day 12)
• Cytotrophoblasts
  • Uteroplacental circulation
  • Anchoring and floating villi
  • Primary Villi
    • cytotrophoblast
  • Secondary Villi
    • cytotrophoblast + extraembryonic mesoderm
  • Tertiary Villi
    • cytotrophoblast + extraembryonic mesoderm+ blood vessels
• initially cover conceptus, then restricted
  • chorion laeve (=smooth)
  • chorion frondosum (=leafy)
• Placenta
  • will cover Embryology and Histology (lecture 13)
  • chorion frondosum and decidua basalis forms the Placenta
  • visible by week 12
  • placenta (= cake)
  • Hydatidiform Mole
  • placenta only, no embryo
  • .5 and 2.5/1000 pregnancies
• Embryoblast- Bilaminar Embryo
  • Inner cell mass
    • before implantation complete forms 2 cell layers
• Bilaminar Embryo
  • Epiblast
    • closest to trophoblasts
    • columnar epithelium
  • Hypoblast
    • closest to blastocoel
    • cuboidal epithelium
    • forms extraembryonic mesoderm
• Bilaminar Embryo-Epiblast
  • cavity forms between cytotrophoblasts and Epiblast
  • cells from epiblast migrate and form wall of cavity
  • Amnionic sac
  • will eventually cover entire embryo
• Implantation Day 8
• Bilaminar Embryo-Hypoblast
  • cells from hypoblast migrate around the blastocoel
  • these cells become extraembryonic mesoderm and line cavity
  • form Primary Yolk sac
• Implantation Day 9
• The 3 Chamber Conceptus
• Extraembryonic mesoderm
  • innermost cell layer thin and line Primary Yolk sac
  • Heuser's membrane
  • outer mesoblasts proliferate, thick
  • surround the amniotic cavity
  • develop spaces around Primary yolk sac
    • spaces fuse to form single cavity
  • extraembryonic coelom (cavity)
  • mesoderm is split by cavity
    • Chorion
      • outer part together with cytotrophoblasts
    • chorionic cavity is 3rd chamber
  • Connecting stalk
    • inner part covers amnion and Primary Yolk sac
• Implantation Day 15
• Implantation Day 16
• Trilaminar Embryo
• Gastrulation
  • process of cell migration from epiblast (day 15)
  • cells migrate through Primitive streak
  • Primitive streak consists of
    • primitive groove
    • primitive pit
    • primitive node
  • Primitive streak defines body axis
    • rostrocaudal (head tail)
    • Left Right
• Primitive Streak- Membranes Day 14
• Trilaminar Embryo-Gastrulation
  • Early cells migrate form Endoderm
    • lie adjacent to epiblast
    • line Primary Yolk sac to form Yolk Sac
    • "Mark's left hand model"
  • Later cells migrate for Mesoderm
    • intraembryonic mesoderm
    • migrate laterally, rostrally, caudally
    • continues until week 4
  • ECM adhesive pathways
• Germ Cell Layers
  • Ectoderm
    • nervous system, epidermis epithelia
  • Mesoderm
    • muscle, skeleton, connective tissue
  • Endoderm
    • gastrointestinal tract epithelia, GIT organs
• Ectoderm/Endoderm Membranes

  • Rostrocaudal axis
  • ectoderm and endoderm without mesoderm
  • form ends of gut tube

• Buccopharyngeal membrane
  • Rostral (head)
  • breaks down to form oral cavity
• Cloacal membrane
  • Caudal (tail)
  • breaks down to form anus, urinary and genital openings
• Axial Process
  • begins at the primitive node
  • hollow tube extends rostrally, beneath the ectoderm
  • stops at the buccopharyngeal membrane
  • notochordal process and endoderm fuse- notochordal plate
  • canal opens between amnion and yolk sac- neurenteric canal
  • notochordal plate and endoderm interact
  • cells rise into mesoderm as a solid rod- notochord
• Trilaminar Embryo- Axial Process
• Sex Determination
  • Please Note- This should have been included in Lecture 1
  • based upon whether an X or Y carrying sperm has fertilized the egg
  • should be 1.0 sex ratio
    • is actually 1.05, 105 males for every 100 females.
  • some studies show more males 2+ days after ovulation
  • cell totipotential
  • Men- Y Chromosome
    • carries sry gene
  • gene activates pathway for male gonad
  • Women- X Chromosome
    • one X chromosome in each cell has to be inactivated.

References

Links: Journals | Textbooks | Online Textbooks | Search Textbooks | Reviews | Articles | Search PubMed | Glossary

Specific references can also be found on each notes page and Selected References 1999

Journals

Textbooks

Human Embryology (2nd ed.) Larson Chapter 1 p1-32

The Developing Human: Clinically Oriented Embryology (8th ed.) Moore and Persaud, Chapter 3 pp42-53

Before we Are Born (5th ed.) Moore and Persaud Chapter 4 pp47-61

Essentials of Human Embryology Larson Chapter 1 p1-16

Human Embryology Fitzgerald and Fitzgerald

UNSW Embryology Selected References 1999

Online Textbooks

Developmental Biology (6th ed) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000. Figure 11.24. Implantation of the mammalian blastocyst into the uterus | Early Mammalian Development

Search NLM Online Textbooks "blastocyst implantation" : Developmental Biology | Endocrinology | Molecular Biology of the Cell | The Cell- A molecular Approach

Reviews

Kodaman PH, Taylor HS Hormonal regulation of implantation. Obstet Gynecol Clin North Am. 2004 Dec;31(4):745-66, ix. Review.

Articles

Güney M, Erdemoglu E, Oral B, Karahan N, Mungan T. Leukemia inhibitory factor (LIF) is immunohistochemically localized in tubal ectopic pregnancy. Acta Histochem. 2008 Feb 6;

Hu W, Feng Z, Teresky AK, Levine AJ. p53 regulates maternal reproduction through LIF. Nature. 2007 Nov 29;450(7170):721-4.

Ralston A, Rossant J. How signaling promotes stem cell survival: trophoblast stem cells and shp2. Dev Cell. 2006 Mar;10(3):275-6.

Yang W, Klaman LD, Chen B, Araki T, Harada H, Thomas SM, George EL, Neel BG. An Shp2/SFK/Ras/Erk Signaling Pathway Controls Trophoblast Stem Cell Survival. Dev Cell. 2006 Mar;10(3):317-27.

Search Feb 2008 "blastocyst implantation" 7,336 reference articles of which 1,029 were reviews.

Search PubMed: term = blastocyst implantation | week 2 embryonic human development | implantation |

Glossary of Terms

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 | Old Glossary

Quick Links

Week 2 Pages:

Introduction | Timeline Week 2 | Carnegie stages 5 to 7 | Abnormalities | Blastocyst Implantation | Sites of Implantation | Bilaminar Embryo | Embryonic Cavitites | Early Placentation | Molecular | Stem Cells | References | Text only | WWW Links | Movies - Week 2

Development Notes ----------------- Menstrual Cycle Week 1 Week 2 Week 3 Week 4 Placenta Serial Images Molecular Dev Abnormal Dev Postnatal Dev Notes Index

System Notes ----------------- All Systems Heart/Cardiovascular Respiratory Coelomic cavity Gastrointestinal Tract Head and Neck Neural Neural Crest Eye Ear Nose Endocrine Renal Genital Musculoskeletal Integumentary

Movies ----------------- Movies Quicktime Flash Audio Week 1 Week 2 Week 3 Stage 13 Stage 22 Neural Heart Gastrointestinal Renal Genital Other Embryos

Other Embryos ----------------- All Animals Chicken Fly Frog Mouse Rabbit Rat Worm Zebrafish Guinea Pig

UNSW Embryology ISBN: 978 0 7334 2609 4

UNSW CRICOS Provider Code No. 00098G