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Embryology is the study of the development of the embryo and the journey from fertilisation of the egg to the formation of a baby. This is an amazingly complex and delicate process which has impacts on the future health and wellbeing of a child. This article looks to provide an introduction to some key concepts in embryology and introduce key events in the first few weeks of development.
All timings given in this article are approximate and are given in embryological age rather than gestational age. Gestational age is calculated from the mother’s last menstrual period, whereas embryological age is calculated from fertilisation. In practice, this means that gestational age is embryological age + 2 weeks.
It is also important to note that most of the development explained in this article occurs before a patient would clinically be pregnant and before a pregnancy test would be positive. This is because pregnancy tests rely on a hormone called beta-human chorionic gonadotropin (beta-hCG), which is produced by the placenta which does not develop until after implantation.
The development of the embryo can be divided into 3 stages.
Germinal Stage: Fertilisation – 2 weeks.
Embryonic Stage: 3-8 weeks.
Fetal Period: 9 weeks – term.
Fertilisation is the process of fusion between the egg and the sperm. Fertilisation occurs when sperm meet the egg in the fallopian tubes, specifically in the ampulla.
Following fertilisation, the first stage of cellular division occurs, with the initial one cell dividing into two daughter cells through the process of mitosis (for more information on this process, see here). The two daughter cells will then divide again into 4 cells which will then themselves divide into 8, then 16, then 32, and so on. Once the bunch of cells divides enough to be made up of 16 cells, it is known as the morula. The word ‘morula’ is Latin for ‘mulberry’ because the embryo at this stage resembles this fruit (it looks similar to a raspberry or a blackberry).
In the next few days, the morula continues to divide and becomes known as the blastocyst. The blastocyst has a spherical shape and is made up of approximately 100 cells. These cells differentiate into two cell lines: the trophoblast and the embryoblast.
The outer cell mass is called the trophoblast. This tissue’s function is to make contact with the endometrium of the uterus and regulate implantation into the uterine wall. Descendants of this structure go on to form the placental tissue.
The inner cell mass is called the embryoblast. This tissue is responsible for the development of the embryo itself.
At this point, the blastocyst is still inside the zona pellucida, the thick glycoprotein layer that surrounded the egg cell as it was released from the ovary. The blastocyst is replicating and increasing in volume, meaning it needs to implant into the uterine wall, and the thick glycoprotein layer is preventing this from happening. The zona pellucida will break open to release the blastocyst in a process called ‘hatching’.
Summary of Week 1
- Fertilisation
- Divisions into the morula (16 cells)
- Divisions into the blastocyst (~100 cells)
- Differentiation of the blastocyst into the trophoblast and embryoblast
- Hatching from the Zona Pellucida.
During the second period of development, the trophoblast and the embryoblast differentiate into specialised cell types:
- The trophoblast differentiates into the syncytiotrophoblast and the cytotrophoblast.
- The embryoblast differentiates into the epiblast and the hypoblast. The epiblast and the hypoblast together form a structure called the bilaminar disk.
Around day 6, the blastocyst must implant in the wall of the uterus. During this process, the syncytiotrophoblast invades into the endometrium, allowing maternal blood vessels to invade into it, forming the basis of the placenta.
Ideally, implantation happens on the posterior, superior wall of the uterus, as this is the best place for the placenta to develop, but it can happen anywhere. If it occurs inferiorly in the uterus, it can block the cervix with the developing placenta, meaning that a fully grown baby would need to push through the placenta to be born vaginally. This is a condition is called placenta previa (literally ‘placenta first’), and this baby needs to be delivered through Caesarean section to avoid haemorrhage.
Up until this point the embryo has relied on histotrophic nutrition, nutrition which is not derived from the maternal blood supply. After the placenta develops the embryo will swap to haemotrophic nutrition, nutrition derived from the maternal blood.
Towards the end of the second week, the hypoblast differentiates into the primary yolk sac and the chorion.
The primary yolk sac is a membranous sac attached to one side of the epiblast. It is important for blood supply, and much of it is incorporated into the development of the gastrointestinal system in later development (around week 4).
The chorion is a membrane that develops from an outer fold of the yolk sac. It fuses with other structures (like the amnion, a small sac-like structure that will form from the mesoderm in around week 4) to form the amniotic sac.
Summary of Week 2
- Trophoblast differentiates to form the syncytiotrophoblast and the cytotrophoblast.
- Embryoblast differentiates to form the epiblast and the hypoblast, which form the bilaminar disk.
- Syncytiotrophoblast invades the endometrium to form the start of the placenta.
- Hypoblast differentiates to form the yolk sac and the chorion.
By the third week, the bilaminar disk undergoes a complicated process called gastrulation. During this process, the bilaminar disk reorganises to start to develop the precursors to recognisable organ systems.
A new feature develops on the dorsal surface of the epiblast called the primitive streak. This is a line of cells formed by the epiblast that establishes orientation; cephalo-caudal (head to tail) and antero-posterior (front to back). It also helps establish symmetry, making sure that the two sides of the embryo are symmetrical. At the cranial end of the primitive streak forms the primitive node, which organises neurulation.
Under the direction of the primitive streak, the epiblast differentiates into three layers: the ectoderm, the mesoderm, and the endoderm, which become known as the trilaminar disk.
These three layers go on to form the structures of the body:
The endoderm becomes the internal layer of the body and forms:
- The lining of internal organ systems:
- Respiratory
- Reproductive
- Urinary
- Gastrointestinal
- Specialised cells:
- Pancreas
- Liver
- Thyroid
The mesoderm becomes the supportive tissues of internal structures:
- Cardiac muscle
- Skeletal muscle
- Smooth muscle of the gut and the circulatory system
- Red blood cells
- Notochord – important in development, see later
By the end of week 3, the mesoderm has spread throughout the other structures formed, like the yolk sac, chorion, and the amnion (that small sac mentioned earlier) to form a supportive layer. This process can be seen on the part of the below diagram labelled ‘Day 18’, and results in the formation of a ‘connecting stalk’ which will progress to be the umbilical cord.
The mesoderm also produces the notochord, a linear structure formed cranio-caudally down the dorsal side of the embryo (meaning it sits where the spine will be). This is a specialised tissue that secretes the growth factors that drive neurulation, the beginning of the development of the central nervous system.
The ectoderm becomes external or neurological structures:
- Epidermal skin cells
- Neurones
- Pigmented cells, like those found on the retina
Diagram - The cell types which develop from each layer of the trilaminar disc
Creative commons source by CNX [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Summary of Week 3
- Gastrulation begins and the primitive streak forms.
- Epiblast differentiates into the endoderm, mesoderm, and ectoderm.
- Mesoderm spreads to surrounding structures, forming the connecting stalk and the notochord.
The fourth week is dominated by three main processes:
- Neurulation – the formation of the neural tube that will go on to become the nervous system.
- Segmentation – the organisation of somites to form repeating structures.
- Folding – the literal folding of the embryo to turn the trilaminar disk into the right shape.
The process of neurulation and the further development of the nervous system will be explained in our article Development of the Nervous System (found here), and so will not be explained in this article.
Segmentation is a process that is driven by somites, which are blocks of mesoderm that run down both sides of the neural tube. Due to their relationship with the neural tube, they are also known as paraxial mesoderm. The somites develop in a cranio-caudal sequence until there are 44 pairs by the end of week 3. Some somites regress leaving 31 somites on either side of the neural tube.
The somites have many derivatives:
- The first derivative to specialise from the somites is the sclerotome. This section of each somite helps to form bones such as the vertebrae and the ribs.
- The second derivative is the dermatomyotome, which quickly splits into a dermatome and a myotome. These help form the skin and muscles of the body respectively.
Because somites are associated so closely with the neural tube, dermatomyotomes are associated with specific levels of the neural tube and specific spinal nerves when they develop. This association explains the pattern of innervation of the spinal nerves in adults.
There are 31 somites, which result in
- 31 vertebrae (there are not 31 vertebrae in the adult as some fuse by birth to form the sacrum and coccyx).
- 31 spinal nerves supplying various muscular functions and sensation to the skin in the form of 31 myotomes and 31 dermatomes.
For more information on dermatomes and myotomes, see the article from our MSK segment found here.
Folding is the process that turns the trilaminar disk into the shape of an embryo by drawing in the edges of the disk. Two folds occur, cephalocaudal folding (at the tail and head), and lateral folding (from both sides). By this point, the neural tube has already formed from the neural plate.
When folding begins, the ‘sides’ of the ectodermal layer fold towards each other on the sagittal plane, called the Lateral Fold, forming the trilaminar disk into a tube with the ectoderm on the outside and the endoderm in the middle of the tube. This movement ‘pinches’ off a portion of the yolk sac that ends up in the middle of the tube shape, and this goes on to become the gastrointestinal tract (GI tract) of the embryo.
There are also cephalocaudal folds at the top and bottom of the embryo to form the beginnings of the head and tail of the embryo. As the cephalocaudal fold does not join in the middle there is still a communication between the developing GI tract and the umbilical cord. This will be explained fully in our development of the GI tract article.
See the diagram below to see these changes in action.
Diagram - The stages in the folding of an embryo. It shows the cephalocaudal fold (transverse) and the lateral fold (sagittal)
SimpleMed original by Maddie Swannack
This image shows the progression from fertilisation, through implantation to the formation of the bilaminar disk, the differentiation into the trilaminar disk, and the eventual folding of the embryo.
Diagram - The first few weeks of human embryogenesis
Creative commons source by Zephyris [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
After this point, the organ systems begin to develop. They all have their own article to explain their development, found below:
- Development of the Cardiovascular System
- Development of the Reproductive Systems
- Development of the Gastrointestinal Tract
- Development of the Urinary Tract
- Development of the Head and Neck
- Development of the Nervous System
- Development of the Respiratory System
Edited by: Dr. Ben Appleby
Reviewed by: Dr. Thomas Burnell
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