First, Second, and Third Week of Embryogenesis

Written by: Adnan Mousa, M.D.

Keywords: Fertilization, Cleavage, Morula Formation, Blastocyst, Implantation, Trophoblast, Bilaminar Disc, Gastrulation, Trilaminar Germ Disc, Notochord.

Overview

The first three weeks of embryogenesis lay the foundation for the development of the human embryo. In week 1, fertilization occurs, followed by cleavage and morula formation, which leads to the blastocyst stage. The blastocyst then implants into the uterine wall. In week 2, the embryo forms the bilaminar disc, consisting of the epiblast and hypoblast, while the trophoblast develops into cytotrophoblast and syncytiotrophoblast layers. Week 3 is pivotal as gastrulation occurs, transitioning the bilaminar disc into a trilaminar disc. The three primary germ layers—ectoderm, mesoderm, and endoderm—form, which give rise to all body tissues. This week also marks the formation of the notochord, a critical structure for axial development.

Fertilization: Week 1 of Embryogenesis

Definition: Fertilization is the process where a sperm and an egg fuse to form a single-cell zygote. 

Location: It occurs in the ampulla of the uterine tube, the widest part near the ovary.

Sperm journey:

• Of the millions of sperm deposited in the vagina, only 300-500 reach the ampulla.

• Sperms move to the uterine tube through uterine contractions, not their own propulsion.

• Before fertilizing the egg, sperm undergo capacitation, a process in the female reproductive tract where their membranes are modified to allow penetration of the egg.

Phases of fertilization:

1. Penetration of the corona radiata: Capacitated sperm pass through the outer cell layer of the egg.

2. Penetration of the zona pellucida: The sperm release enzymes (acrosome reaction) to break through the egg's glycoprotein shell.

3. Fusion of membranes: The sperm and egg membranes fuse, allowing the sperm's nucleus to enter the egg.

Key outcomes:

• Restoration of diploid chromosomes: 23 chromosomes from each parent combine, forming 46 chromosomes.

• Sex determination: The sperm determines the sex—X sperm creates a female (XX), Y sperm creates a male (XY).

• Initiation of cleavage: The zygote begins rapid cell division, essential for early embryonic development.

Figure 1. Fertilization in the fallopian tube.

Blausen.com staff. (2014). Medical gallery of Blausen Medical 2014. WikiJournal of Medicine, 1(2). https://doi.org/10.15347/wjm/2014.010

BruceBlaus. (2013, November 20). Fertilization. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Blausen_0404_Fertilization.png

Figure 2. Sperm entering the ovum.

Atdoan0. (2018, May 30). Sperm entering the ovum using the acrosome, which breaks down the zona pellucida with enzymes. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:The_sperm_and_ovum_during_fertilization.svg

Figure 3. Fertilization in detail.

Sciencia58. (2019, October 10). Fertilisation phases of a human egg. The middle part of the sperm with mitochondria of the father remains outside the zygote. The mitochondria of the mother are already in the oocyte. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Egg_cell_fertilization_-_Zygote.png

Week 1: Cleavage and Morula Formation

• Cleavage:

  • Starts at the two-cell stage, around 30 hours after fertilization.

  • Rapid mitotic divisions increase cell numbers but do not increase size; cells become smaller with each division.

  • These small cells are called blastomeres.

  • By the eight-cell stage, blastomeres undergo compaction, forming a tightly connected ball of cells held together by tight junctions.

  • At around 3 days post-fertilization, the compacted embryo divides further to form the morula, a 16-cell structure resembling a mulberry.

• Inner and outer cell mass:

  • The inner cell mass of the morula becomes the embryo proper.

  • The outer cell mass becomes the trophoblast, contributing to placenta formation.

Figure 4. Stages of embryo development.

Zephyris. (2010, July 5). The first few weeks of embryogenesis in humans. Beginning at the fertilised egg, ending with the closing of the neural tube. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:HumanEmbryogenesis.svg

Week 1: Blastocyst Formation

• Fluid accumulation:

  • At day 4, fluid enters the morula, forming a cavity called the blastocele.

  • The structure is now termed a blastocyst.

• Components:

  • Inner cell mass (embryoblast): Positioned at one pole, forms the embryo.

  • Trophoblast: Outer layer that forms the wall of the blastocyst and later aids implantation.

Week 1: Implantation

• Begins around day 6 when the blastocyst attaches to the uterine lining (endometrium).

• Trophoblast role:

  • Cells of the trophoblast secrete molecules that allow attachment and penetration into the endometrium.

  • Facilitates nutrient exchange and further implantation.

Figure 5. Stages of fertilization.

OpenStax College. (2013, June 19). Illustration from Anatomy & Physiology, Connexions Web site. Embryonic Development. OpenStax. https://commons.wikimedia.org/wiki/File:2904_Preembryonic_Development-02.jpg

Week 2: Bilaminar Disc and Early Placenta Formation

Trophoblast differentiation:

• The trophoblast divides into two layers:

  • Cytotrophoblast: The inner layer with actively dividing cells. These cells migrate outward to form the syncytiotrophoblast.

  • Syncytiotrophoblast: The outer layer without distinct cell boundaries. It invades maternal tissues and plays a key role in implantation and early blood supply.

Formation of the bilaminar embryonic disc:

The inner cell mass (embryoblast) forms two distinct layers:

• Epiblast: A layer of columnar cells that will give rise to the embryo. It forms the roof of the amniotic cavity.

• Hypoblast: A layer of cuboidal cells that contributes to forming the yolk sac.

Development of extraembryonic structures:

• Amniotic cavity: A fluid-filled space forms above the epiblast and is lined by amnioblasts (specialized epiblast cells).

• Yolk sac formation: The hypoblast and surrounding cells create the primitive yolk sac, which provides early nutrients to the embryo.

• Extraembryonic mesoderm: A layer of connective tissue that arises between the trophoblast and the yolk sac and amniotic cavity. It supports the embryo and forms the basis for the chorionic cavity.

• Chorionic cavity: Large spaces form in the extraembryonic mesoderm, merging to create the chorionic cavity, surrounding the yolk sac and amniotic cavity.

Primary placenta formation:

• Lacunae development: Small spaces in the syncytiotrophoblast fill with maternal blood. These lacunae connect to maternal sinusoids (blood vessels), establishing the first uteroplacental circulation.

• Connecting stalk: The structure that will later develop into the umbilical cord forms within the chorionic cavity.

Notes:

• The second week is called the “week of 2’s”: Two layers form in the trophoblast (cytotrophoblast and syncytiotrophoblast), embryoblast (epiblast and hypoblast), and extraembryonic mesoderm (somatic and splanchnic).

• Implantation completes as the blastocyst becomes fully embedded in the uterine lining, and the surface defect is sealed.

Figure 6. Trophoblast differentiation.

OpenStax College. (2013, June 19). Illustration from Anatomy & Physiology, Connexions Web site. Embryonic Development. OpenStax. https://commons.wikimedia.org/wiki/File:2907_Embroyonic_Disc,_Amniotic_Cavity,_Yolk_Sac-02.jpg

Figure 7. Yolk sac and connecting stalk.

Gray, H. (1918). Section through the embryo which is represented in Fig. 17. (After Graf Spee.) Plate 21. In Anatomy of the Human Body. Bartleby.com. https://commons.wikimedia.org/wiki/File:Gray21.png

Third Week of Development: Trilaminar Germ Disc

Introduction:

• The third week of development marks a critical transition from a bilaminar (two-layered) to a trilaminar (three-layered) embryo.

• This transformation happens through gastrulation, a process that establishes the three primary germ layers that give rise to all tissues and organs in the body.

Formation of the trilaminar germ disc:

• The three primary germ layers formed during this week are:

  • Ectoderm: The outer layer that will form the skin, brain, and spinal cord.

  • Mesoderm: The middle layer that will form muscles, bones, kidneys, and the cardiovascular system.

  • Endoderm: The inner layer that will form the gastrointestinal and respiratory systems.

Key processes in gastrulation:

• Gastrulation begins with the formation of the primitive streak at the caudal end of the epiblast. This streak marks the site where cells will begin to migrate inward, undergoing a process called invagination.

• As cells from the epiblast move inward, they form:

  • Mesoderm: Cells that move between the epiblast and hypoblast layers.

  • Endoderm: Cells that displace the hypoblast, forming the new inner layer.

  • Ectoderm: The remaining cells of the epiblast that will form the outer layer.

Figure 8. Gastrulation.

Figure 9. Human embryogenesis.

Formation of the notochord:

• Notochord formation starts with prenotochordal cells that migrate through the primitive streak. These cells form a solid cord called the notochord, which acts as a signaling center for the development of the axial skeleton and plays a role in inducing neural development.

Figure 10. Primitive streak and notochord.

Figure 11. Notochord.

Development of the germ layers:

1. Ectoderm: Forms structures like the nervous system (brain, spinal cord) and epidermis (skin).

2. Mesoderm: Develops into muscles, bones, kidneys, and the cardiovascular system (heart, blood vessels).

3. Endoderm: Forms the digestive tract, lungs, and other internal organs (liver, pancreas).

Figure 12. Germ layers.

Establishment of the body axes:

• Primitive streak helps establish the three main body axes:

  • Anterior-posterior (A-P): Head-to-tail axis.

  • Dorsal-ventral (D-V): Back-to-belly axis.

  • Left-right (L-R): Establishes organ asymmetry (e.g., the heart being on the left side).

Figure 13. Body axes.

Blausen.com staff. (2014). Medical gallery of Blausen Medical 2014. WikiJournal of Medicine, 1(2). https://doi.org/10.15347/wjm/2014.010

Blaus, B. (2014). Directional references. https://commons.wikimedia.org/wiki/File:Blausen_0019_AnatomicalDirectionalReferences.png