Week 1

Embryology - 1 Dec 2023        Expand to Translate
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Introduction

Week 1 and 2 development

Key Events of Human Development during the first week (week 1) following fertilization or clinical gestational age GA week 3, based upon the last menstrual period.

The first week of human development begins with fertilization of the egg by sperm forming the first cell, the zygote. Cell division leads to a ball of cells, the morula. Further cell division and the formation of a cavity in the ball of cells forms the blastocyst. These notes also cover events before fertilization formation of both the egg and sperm, gametogenesis.

Initially, there is a halving of chromosomal content in the gametes (spermatozoa and oocyte) by the process called gametogenesis. Chromosomal content is then restored by fertilization, allowing genetic recombination to occur. This is then followed by a series of cell divisions without cytoplasmic growth. During this first week the egg, then zygote, morula then the blastula is moving along the uterine horn into the uterus for implantation in the uterine wall.

Implantation also begins in this first week, but will be covered in Week 2 notes, as the implantation process is completed by the end of the second week.

Carnegie Stages

Week:	1	2	3	4	5	6	7	8
Carnegie stage:	1 2 3 4	5 6	7 8 9	10 11 12 13	14 15	16 17	18 19	20 21 22 23

Historic Carnegie Stages 1 to 4.

Stage 1	Stage 2	Stage 3	Stage 4	Stage 5

Some Recent Findings

Different regulatory mechanisms between mouse and human embryo pre-implantation development "There were differences between mouse and human pre-implantation development both in the global gene expression pattern and in the expression changes of individual genes at each stage, including different major transient waves of transcription profiles and some stage-specific genes and significantly related pathways. There also appeared to be different functional changes from one stage to another between mouse and human."

Reading

Human-oocyte to blastocyst

• Human Embryology (2nd ed.) Larson Chapter 1 pp1-32
• The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud
• Before we Are Born (5th ed.) Moore and Persaud Chapter 2 pp14-33
• Essentials of Human Embryology Larson Chapter 1 pp1-16
• Human Embryology Fitzgerald and Fitzgerald Chapter 2 pp8-14

Week 1 Movies

‎‎Ovulation Page | Play

‎‎Spermatozoa Page | Play

‎‎Spermatozoa Motility Page | Play

‎‎Fertilization Page | Play

‎‎Mouse Fertilisation Page | Play

‎‎Pronuclear Fusion Page | Play

‎‎Week 1 Page | Play

Human Blastocyst

‎‎Day 3 to 6 Page | Play

‎‎Contractions Page | Play

‎‎Hatching Page | Play

Human Blastocyst (day 3 to 6)

‎‎Day 3 to 6 Page | Play

‎‎Contractions Page | Play

‎‎Hatching Page | Play

Human blastocyst week 1 movies, 3 above movies together in single table.

Mouse Zygote

‎‎Mouse Fertilisation Page | Play

‎‎Zygote Mitosis Page | Play

‎‎Early Division Page | Play

‎‎Parental Genomes Page | Play

‎‎Mouse Blastocyst Page | Play

Models

‎‎Morula Model Page | Play

‎‎Blastocyst Model Page | Play

Links: Movies

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

Human zygote pronuclei	Mouse zygote pronuclei

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).

Epigenetics

Within the early zygote, at the 2 pronuclei stage, the male pronucleus is "reprogrammed" by the demethylation of the paternal genome. Image sequence shows the mouse zygote at pronuclear stages, where the male pronucleus initially contains methylcytosine (5mC, red) oxidises to form hydroxymethylcytosine (5hmC, green).

• PN1/PN2 (Early)
• PN3 (Mid)
• PN4/PN5 (Late)

5mC - 5-methylcytosine (red). 5hmC - 5-hydroxymethylcytosine (green) formed by enzymatic oxidation of 5mC.

Links: Epigenetics | Figure 8.19. Changes in DNA methylation during mammalian development

Cleavage of Zygote

Mouse zygote mitosis

First metaphase	First anaphase

Cleavage of the zygote forms 2 blastomeres and is cleavage with no cytoplasm synthesis.

• special "embryonic" cell cycle S phases and M phases alternate without any intervening G1 or G2 phases (MSMSMSMS, adult MG1SG2) therefore individual cell volume decreases

Cell division within these cells is initially synchronous (at the same time), then becomes asynchronously (at different times).

• slow- centre cells, larger fast- peripheral cells

Links: Zygote | Cell Division - Mitosis | Movie - Week 1 Cell Cleavage | Carnegie stage 1

Morula

Human morula (day 2)

Carnegie stage 2

• about day 4 is a solid ball of 16-20 cells with peripheral cells flattened against zona pellucida
• compaction occurs forming a cavity and leading to the next blastocyst stage

Links: Morula | Figure 8.19. Changes in DNA methylation during mammalian development

Blastocyst

Carnegie stage 3

Hatching Blastocyst

• about day 5 have 2 identifiable cell types and a fluid-filled cavity (blastoceol)
  • trophoblast layer - peripheral flattened cells, forms the placenta and placental membranes
  • inner cell mass - embryoblast, mass of rounder cells located on one wall of the blastocoel, forms entire embryo

Blastula Cell Communication

Two forms of cellular junctions Figure 21-69. The blastula

• gap junctions, allow electrically couple cells of epithelium surrounding a fluid-filled cavity
• tight junctions, close to outer surface create a seal, isolates interior of embryo from external medium

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: Blastocyst Development | Carnegie stage 3

Summary of the first week following fertilization

<html5media height="260" width="660">File:Week1_001.mp4</html5media> Click Here to play on mobile device

‎‎Week 1 Page | Play

The conceptus proceeds through embryonic cell cycle rounds of mitosis still enclosed within the zona pellucida. Progressing from a zygote, to blastomeres, then to a morula and finally to a blastocyst. The uterine tube epithelium consists of ciliated cells that are moving the secreted fluid towards the uterine body. The conceptus is floating "boat-like" within this fluid and moved in the same direction. Towards the end of the first week the blastocyst has reached the uterine body and from about day 5 onwards, the blastocyst "hatches" from the surrounding zona pellucida. The conceptus can now receive nutrition directly and can commence the process of implantation in week 2.

Molecular Changes

There are several important changes that occur in this new diploid cell beginning the very first mitotic cell divisions and expressing a new genome.

The oocyte arrested in meiosis is initially quiescent in terms of gene expression, and many other animal models of development have shown maternal RNAs and proteins to be important for early functions.

The new zygote gene expression is about cycles of mitosis and maintaining the toptipotency of the stem cell offspring cells.

The morula gene expression supports the formation of two populations of cells the trophoblast (trophectoderm) and embryoblast (inner cell mass), each having different roles in development, while maintaining the toptipotency of these populations.

Current research is now also pointing to non-genetic mechanisms or epigenetics as an additional mechanism in play in these processes.

Links: Cell Division - Mitosis | Molecular Development - Epigenetics

Genome Expression

The following figure is from a recent study 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 | Blastocyst Quicktime Movie | Blastocyst Flash Movie

Telomere Length

A recent paper has measured telomere length in human oocyte (GV, germinal vesicle), morula and blastocyst and found changes in this length in preimplantation embryos. Telomeres are the regions found at the ends of each chromosome and involved in cellular ageing and the capacity for division. The regions consist of repeated sequences protecting the ends of chromosomes and harbour DNA repair proteins. In the absence of the enzyme telomerase, these regions shorten during each cell division and becoming critically short, cell senescence occurs.

Early human telomeres	Early human telomere length

Timeline

Day	Stage	Event
1	Secretory Phase Stage 1	Fertilization, Zygote, Secretory Phase
2	Stage 2	Morula, Blastula
3
4
5	Stage 3	Blastocyst Hatching (zona pellucida lost) Blastocyst (free floating)
6	Stage 4	Adplantation
7	Stage 5	Implantation

Week 1 Movies

Ovulation	Fertilization	Pronuclear Fusion	Week 1	Ovulation in the rabbit	Fertilization in the mouse

Week 1 Abnormalities

See Week 1 - Abnormalities

Dizygotic Twinning

Dizygotic twins (fraternal, non-identical) arise from separate fertilization events involving two separate oocyte (egg, ova) and spermatozoa (sperm).

Monoygotic Twinning

Monozygotic twins (identical) produced from a single fertilization event (one fertilised egg and a single spermatazoa, form a single zygote), these twins therefore share the same genetic makeup. Occurs in approximately 3-5 per 1000 pregnancies, more commonly with aged mothers. The later the twinning event, the less common are initially separate placental membranes and finally resulting in conjoined twins.

Week		Week 1							Week 2
Day	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14
Cell Number	1	1	2	16	32	128				bilaminar
Event	Ovulation	fertilization	First cell division	Morula	Early blastocyst	Late blastocyst Hatching	Implantation starts			X inactivation
Monoygotic Twin Type		Diamniotic Dichorionic			Diamniotic Monochorionic			Monoamniotic Monochorionic			Conjoined

Table based upon: Twinning. Hall JG.

References

Niakan KK & Eggan K. (2013). Analysis of human embryos from zygote to blastocyst reveals distinct gene expression patterns relative to the mouse. Dev. Biol. , 375, 54-64. PMID: 23261930 DOI.

Embryo Week: Week 1 | Week 2 | Week 3 | Week 4 | Week 5 | Week 6 | Week 7 | Week 8 | Week 9

Carnegie Stages: 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | 23 | About Stages | Timeline

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

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Cite this page: Hill, M.A. (2023, December 1) Embryology Week 1. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Week_1

What Links Here?

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