THE DEVELOPMENT OF EMBRYO
#WEEK 1
Day 1. Fertilization
In the beginning is the egg. Inside the fallopian tube, a mature human egg waits in a state of arrested development. Just released from the ovary, it is the largest cell in the human body. The egg is packed with nutrients, growth factors, enzymes and proteins — nearly everything it needs to jump start the development of a human embryo. Except for one little thing — it needs a sperm. If a sperm doesn’t penetrate the egg’s tough outer membrane to activate it within the next 24 hours, the egg will die.¬¬
The sperm cells contain the male genetic contribution to the new genome that will be produced at the completion of fertilization. Sperm cells are produced during the process of meiosis, which occurs in the testis during spermatogenesis. At the completion of meiosis each sperm contains a haploid genome (one chromatid from each chromosome pair).
During fertilization and the first stage of embryonic development, the egg runs the show. All a mature human egg really needs from a sperm is its DNA — the genetic code stored in 23 chromosomes inherited from the father. When combined with 23 chromosomes in the egg from the mother, the new embryo has the full complement of genetic material required to make a human being.
The fertilization process commences with the sperm initiating the penetration of the zona pellucid. Firstly, the sperm squeezes through cells left over from the follicle. When it reaches the jelly coat, the sperm’s acrosomal enzymes digest the egg’s jelly coat to reveal receptor protein molecules of the egg. Then, proteins on the sperm head bind to egg receptors and the Plasma membranes of the sperm and egg fuse. The sperm nucleus enters the egg cytoplasm. After that, the egg nucleus and sperm nucleus meet, the nuclei of sperm and egg fuse together to make to zygote nucleus.
Day 2 to 3: Cleavage stage
Inside the mother’s body, a fertilized egg moves through the fallopian tube, pushed toward the uterus by filaments lining the inside of the tube. Still dependent on nutrients and genetic instructions contributed by the egg, the embryo divides to form two cells, then four cells, eight cells and then lastly, sixteen cells. The cell division at this stage is called cleavage since furrows appear as the cytoplasm divides. The daughter cells are called blastomeres. An embryo with 16 – 32 cells called a morula.
Day 3 to 5: Blastulation
Cleavage itself is the first stage in blastulation, the process of forming theblastocyst. Cells differentiate into an outer layer of cells (collectively called thetrophoblast) and an inner cell mass. With further compaction the individual outer blastomeres, the trophoblasts, become indistinguishable, and are still enclosed within the zona pellucida. This compaction serves to make the structure watertight since the cells will later secrete fluid. The inner mass of cells differentiate to become embryoblasts and polarise at one end. They close together and form gap junctions in order to facilitate cellular communication. This polarisation leaves a cavity, the blastocoel in which is now termed the blastocyst. (In animals other than mammals, this is called the blastula). The trophoblasts secrete fluid into the blastocoel. By this time the size of the blastocyst has increased which makes it 'hatch' through the zona pellucida which then disintegrates.
The inner cell mass will give rise to the embryo proper, the amnion, yolk sac and allantois, while the fetal part of theplacenta will form from the outer trophoblast layer. The embryo plus its membranes is called the conceptus and by this stage the conceptus is in the uterus. The zona pellucida ultimately disappears completely, and the now exposed cells of the trophoblast allow the blastocyst to attach itself to the endometrium, where it will implant. The formation of thehypoblast and epiblast occurs at the beginning of the second week, which are the two main layers of the bilaminar germ disc. Either the inner cells embryoblast or the outer cells trophoblast will turn into two sub layers each other. The inner cells will turn into the hypoblast layer that will surround the other layer called epiblast layer, and these layers will form the embryonic disc in which the embryo will develop. The place where the embryo develops is called the amniotic cavity, which is the inside the disc. Also the trophoblast will develop two sub-layers; the cytotrophoblast that is front of the syncytiotrophoblast that is inside of the endometrium. Next, another layer called the exocoelomic membrane or Heuser’s membrane will appear and surround the cytotrophoblast, as well as the primitive yolk sac. The syncytiotrophoblast will grow and will enter a phase called lacunar stage, in which some vacuoles will appear and be filled by blood in the following days. The development of the yolk sac starts with the hypoblastic flat cells that form the exocoelomic membrane, which will coat the inner part of the cytotrophoblast to form the primitive yolk sac. An erosion of the endothelial lining of the maternal capillaries by the syncytiotrophoblastic cells of the sinusoids will form where the blood will begin to penetrate and flow through the trophoblast to give rise to the uteroplacental circulation. Subsequently new cells derived from yolk sac will be established between trophoblast and exocelomic membrane and will give rise to extra-embryonic mesoderm, which will form cavities known as chorionic cavity.
At the end of the second week of development, some cells of the trophoblast penetrate and form rounded columns into the syncytiotrophoblast. These columns are known as primary villi. At the same time, other migrating cells form into the exocelomic cavity a new cavity named as secondary or definitive yolk, smaller in size than the primitive yolk sac.
Day 6 – 7: Implantation
The Embryo attaches to wall of uterus. Reserved for the attaching blastocyst that is adhering to the endometrial lining of the uterus. The attaching process is called adplantation and heralds the onset of implantation. The embryos have an estimated postfertilization age of approximately 6 days. Because there are no known in vivohuman specimens at this stage, the stage is represented by in vitro human specimens and one rhesus specimen.
The implantation: Implantation is the process whereby the early embryo embeds into the inner wall of the mother’s uterus. Implantation begins about 6 days after fertilization and is complete by about 12 days.
The first step of this process is the attachment phase, which begins about 6 days after fertilization. The outer cells (trophoblast cells) of the blastocyst have specialized adhesion molecules which bind to the epithelial cells of the endometrium. The cells in the uterine wall are full of nutrients and water. The blastocyst attaches between the uterine glands, along its surface overlying the inner cell mass (the embryonic pole). Once attached. the trophoblast cells release enzymes that digest, liquify, and separate maternal cells forming an entry way inside the uterine wall. The trophoblast cells capture the local nutrients and actively share them with the inner cell mass.
# WEEK 2
Day 12: Bilaminar disc formation
The embryoblast forms an embryonic disc which is a bilaminar disc of two layers, an upper layer the epiblast (primitiveectoderm), and a lower layer the hypoblast (primitive endoderm). The disc is stretched between what will become the amniotic cavity and the yolk sac. The epiblast is adjacent to the trophoblast and made of columnar cells; the hypoblast is closest to the blastocyst cavity, and made of cuboidal cells. The epiblast migrates away from the trophoblast downwards, forming the amniotic cavity, the lining of which is formed from amnioblasts developed from the epiblast. The hypoblast is pushed down and forms the yolk sac (exocoelomic cavity) lining. Some hypoblast cells migrate along the inner cytotrophoblast lining of the blastocoel, secreting an extracellular matrix along the way. These hypoblast cells and extracellular matrix are called Heuser's membrane (or exocoelomic membrane), and they cover the blastocoel to form the yolk sac (or exocoelomic cavity). Cells of the epiblast migrate along the outer edges of this reticulum and form the extraembryonic mesoderm, which makes it difficult to maintain the extraembryonic reticulum. Soon pockets form in the reticulum, which ultimately coalesce to form the chorionic cavity or extraembryonic coelom.
# WEEK 3 TO WEEK 4
Day 16: Gastrulation: Formation of germ layers
The primitive streak, a linear band of cells formed by the migrating epiblast, appears, and this marks the beginning of gastrulation, which takes place around the sixteenth day (week 3) after fertilisation. The process of gastrulation reorganises the two-layer embryo into a three-layer embryo, and also gives the embryo its specific dorsal-ventral and anterior-posterior orientation, by way of the primitive streak which establishes bilateral symmetry. A primitive node (or primitive knot) forms in front of the primitive streak which is the organiser of neurulation. A primitive pit forms as a depression in the centre of the primitive node which connects to the notochord which lies directly underneath. The node has arisen from epiblasts of the amniotic cavity floor, and it is this node that induces the formation of the neural plate which serves as the basis for the nervous system. The neural plate will form opposite the primitive streak from ectodermal tissue which thickens and flattens into the neural plate. The epiblast in that region moves down into the streak at the location of the primitive pit where the process called ingression, which leads to the formation of the mesoderm takes place. This ingression sees the cells from the epiblast move into the primitive streak in an epithelial-mesenchymal transition; epithelial cells become mesenchymal stem cells, multipotent stromal cells that can differentiate into various cell types. The hypoblast is pushed out of the way and goes on to form the amnion. The epiblast keeps moving and forms a second layer, the mesoderm. The epiblast has now differentiated into the three germ layers of the embryo, so that the bilaminar disc is now a trilaminar disc, the gastrula.
The three germ layers are the ectoderm, mesoderm and endoderm, and are formed as three overlapping flat discs. It is from these three layers that all the structures and organs of the body will be derived through the processes of somitogenesis, histogenesis and organogenesis. The embryonic endoderm is formed by invagination of epiblastic cells that migrate to the hypoblast, while the mesoderm is formed by the cells that develop between the epiblast and endoderm. In general, all germ layers will derive from the epiblast. The upper layer of ectoderm will give rise to the outermost layer of skin, central and peripheral nervous systems, eyes, inner ear, and many connective tissues. The middle layer of mesoderm will give rise to the heart and the beginning of the circulatory system as well as the bones, muscles and kidneys. The inner layer of endoderm will serve as the starting point for the development of the lungs, intestine and bladder.
Following ingression, a blastopore develops where the cells have ingressed, in one side of the embryo and it deepens to become the archenteron, the first formative stage of the gut. The blastopore becomes the anus whist the gut tunnels through the embryo to the other side where the opening becomes the mouth. With a functioning digestive tube, gastrulation is now completed and the next stage of neurulation can begin.
Day 18 – 28: Neurulation
Following gastrulation, the ectoderm gives rise to epithelial and neural tissue, and the gastrula is now referred to as the neurula. The neural plate that has formed as a thickened plate from the ectoderm, continues to broaden and its ends start to fold upwards as neural folds. Neurulation refers to this folding process whereby the neural plate is transformed into the neural tube, and this takes place during the fourth week. They fold, along a shallow neural groove which has formed as a dividing median line in the neural plate. This deepens as the folds continue to gain height when they will meet and close together. The cells that migrate through the most cranial part of the primitive line form the paraxial mesoderm, which will give rise to the somitomeres that in the process of somitogenesis will differentiate into somites that will form thesclerotome, the syndetome, the myotome and the dermatome to cartilageand bone, tendons, dermis (skin), and muscle. The intermediate mesoderm gives rise to the urogenital tract and consists of cells that migrate from the middle region of the primitive line. Other cells migrate through the caudal part of the primitive line and form the lateral mesoderm, and those cells migrating by the most caudal part contribute to the extraembryonic mesoderm.
The embryonic disc begins flat and round, but eventually elongates to have a wider cephalic part and narrow-shaped caudal end. At the beginning, the primitive line extends in cephalic direction and 18 days after fertilization returns back caudally until it disappears. In the cephalic portion, the germ layer shows specific differentiation at the beginning of the 4th week, while in the caudal portion it occurs at the end of the 4th week. Cranial and caudal neuropores become progressively smaller until they close completely (by day 28) forming the neural tube.
# WEEK 5
The cells making up the ovum are beginning to differentiate and specialize in areas of development. Some cells will make up the embryo; others the amniotic sac and placenta etc. The ovum, which has been floating around in your uterus, has now implanted into the wall of the uterus. Now comes an exciting time of rapid growth! The amniotic sac, amniotic cavity and yolk sac are developing. The placenta is beginning to form now too.
Implantation - Some spotting (also known as implantation bleeding) may occur about 10 - 14 days after conception. You may believe you are starting your period but generally this spotting (bleeding) is extremely light and lasts only a day or so.
At week five, you might begin to suspect you're pregnant since the embryo produces hormones which stop the mother's menstrual cycle. The fertilized egg, now called a blastocyst, is a fluid-filled cluster of about 500 cells, still multiplying madly. It is attached to the uterus wall and divides into two parts. The half attached to the uterine wall becomes the placenta, the vessel-filled support system that nourishes the developing life, and the other half will become the baby.
At the end of week five; nerve growth begins when a sheet of cells on the back of the embryo folds in the middle to form a tube, which will become the future spinal cord. At one end tube enlarges to form the brain's major sections. The amniotic fluid that cushions the embryo begins to form. Between the forth and fifth week the embryo more than doubles in size to about, 4-5mm about a 1/8 inch in size.
# WEEK 6
Many of your symptoms are the same as last week. Some women may also get headaches from the rise in hormones. There are also a lot of women who will have none of these symptoms. They will sail through early pregnancy without vomiting or being light headed. For a lot of women this can be normal as well. Do not panic if you do not have pregnancy symptoms, although you should contact your care provider if you suddenly lose your pregnancy symptoms. At this time the embryo is still smaller than the size of a raisin. Low on the sides of the head are two folds of tissue that will become the ears. Although not completely developed, all the major body organs and systems are formed. The heart also forms, and it begins to beat on the 25th day after conception (about 6 weeks after the last menstrual period), and a heart beat can already be detected.
The neural tube enlarges into three parts, that will soon to develop to become a very complex brain. Also the placenta begins functioning, known as the chorionic villi and the umbilical cord, through which the baby will receive nourishment and oxygen. The spine and spinal cord grows faster than the rest of the body at this stage and will give the appearance of a tail. This will disappear as the baby continues to grow.
# WEEK 7
The baby's eyes and inner ears are starting to develop. It is about now that your baby's major organs (heart, lungs liver, spleen, and kidneys) are beginning to develop. Your baby's digestive system is becoming more refined as the stomach and intestines develop. Remember the Folic Acid you should be taking? Well, since the Neural tube (later known as spinal cord) begins to fuse, folic acid is important in preventing neural tube defects. The embryo size is about a 1/8 inch (4mm) long.
On the 26th day after fertilization, the embryo's tiny heart begins to beat. Other major organs, including the kidneys and liver, have begun to develop, and the neural tube, which connects the brain and spinal cord, closes. The physical sensations of pregnancy have started--nausea, fatigue, sore breasts and frequent urination.
The embryo's arms and legs begin to grow from buds at each side. At first the hands and feet are shaped like paddles, but the fingers soon take shape. Lenses of the eyes appear - You would notice your baby's appearance is becoming increasing like a newborn's. Brain is growing well