Week One
Overview
The first week of development is devoted to four main activities:
- Fertilization
- Cleavage
- Blastocyst formation
- Implantation
Fertilization
Overview
Fertilization usually occurs in the distal 1/3 of the uterine tube (oviduct), the portion called the ampulla.
- If ovulation has occurred, a secondary oocyte and first polar body, surrounded by a glycoprotein shell, the zona pellucida may be present in the ampulla of the oviduct.
- It is accompanied by several layers of granulose cells, the corona radiata.
- Only capacitated sperm can penetrate the corona radiata and effect fertilization.
- Upon ejaculation, about 200 – 600 million sperm are deposited near the cervical os of the uterus and posterior fornix of the vagina.
- They must travel through the entire female reproductive tract to reach the ampulla of the uterine tube.
- They must endure a period of capacitation before they are capable of fertilizing an ovum.
Capacitation
Capacitation is the conditioning of spermatozoa, preparing them to carry out fertilization.
Capacitation occurs during the 7 hours or so that spermatozoa take to navigate the uterus and uterine tube; much of it taking place in the uterine tube involving interactions between sperm cells and the mucosal cells lining the uterine tube.
It involves removal of seminal plasma proteins and a glycoprotein coat over the acrosome region of the sperm head.
Phases of Fertilization
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Start Slide Show
Capacitated sperm may reach the ampulla of the uterine tube where fertilization usually occurs. Only capacitated sperm can penetrate the corona radiata to contact the zona pellucida.
Acrosome Reaction
Sperm that contact zona pellucida bond to it and undergo acrosome reaction by releasing acrosin, a trypsin like substance that allows penetration of the zona pellucida by the sperm cell.
Fig 1a. Drawing of secondary oocyte surrounded by corona radiata and capacitated sperm. One sperm has begun to erode into zona pellucid by initiating acrosome reaction.
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Once a single sperm penetrates the zona pellucida and contacts the surface of the oocyte, cortical and zonal reactions occur.
Cortical Reaction
Cortical reaction involves release of cortical oocyte granules (lysosomes) making the oocyte membrane impermeable to other sperm cells.
Fig 1b. Drawing of secondary oocyte showing release of cortical granules in response to sperm cell contacting membrane of secondary oocyte.
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Zonal Reaction
Zona reaction alters the structure of the zona pellucida so that no other sperm can bind to it or penetrate it.
This prevents polyspermy.
Fig 1c. Penetration of the sperm cells into initiates completion of meiosis II, forming the ovum and second polar body. At the same time zona reaction makes zona pellucida impermeable to other sperm thus preventing polyspermy.
What is polyspermy?Polyspermy literally means many sperm. Cortical reaction and zonal reaction prevent other sperm from fertilizing the ovum. This assures the zygote will have only two sets of chromosomes or the diploid number after fertilization. -
Completion of Meiosis II
Fusion of the plasma membranes of the oocyte and sperm initiates the completion of the second meiotic division to form the mature ovum and the second polar body.
The sperm nucleus enlarges to form the male pronucleus.
The nucleus of the ovum becomes the female pronucleus.
Each of these pronuclei make a complete set of chromosomes, thus reesetablishing the diploid number of chromosomes.
Fig 1d. Drawing depicting ovum and second polar body at the end on meiosis II. The nucleus of the ovum and sperm swell to form the female and male pronuclei.
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Zygote Formation
Fertilization is complete with the fusion of the male and female pronuclei and re-establishment the diploid number of chromosomes.
The new individual created by fertilization is called a zygote which begins a process of cell division called cleavage.
Fig 1e. Fertilization is complete upon fusion of the male and female pronuclei and the formation of the zygote.
Fusion of male and female pronuclei is a complex, multistep process that is frequently imperfect, resulting in aneuploidy in the embryo and accounting in part for the frequency of spontaneous abortion.
Results of Fertilization
Fertilization accomplishes several changes:
- Zygote formation - Development of a new individual.
- Reestablishment of the diploid number of chromosomes - Maintains the full compliment of chromosomes appropriate to the species.
- Sex determination - The genetic sex of the new individual is determined by whether a Y-chromosome bearing sperm or an X-chromosome bearing sperm fertilized the egg.
- Variation in the species - Since half of the genetic material of the new individual comes from the male parent and half from the female parent, the genetic composition of the new individual reflects both parents.
- Initiation of cleavage - Development of the new individual proceeds with the first mitotic division of the zygote.
Cleavage
Fig 3. Animated GIF showing early cleavage, doubling and compaction from fertilized ovum to blastocyst.
Fig 2. Early cleavage involves cell doubling with each successive division to rapidly increase the number of cells in the zygote.
- Cleavage is the repeated mitotic division of the zygote that results in an increasing number of cells with no increase in cell size.
- The process begins soon after fertilization and continues as the zygote moves down the uterine tube.
- During early cleavage, the cell number doubles with each division, a process called, oddly enough, doubling.
- The daughter cells generated by these divisions are blastomeres.
- Since the zygote is still contained within the zona pellucida, successive generations of blastomeres become progressively smaller or compacted.
Compaction occurs when the zygote reaches the nine cell stage and the blastomeres change shape and tightly align themselves with one another.
This allows for greater cell to cell interaction and subsequent re-aggregation of the cells into inner and outer cell masses.
Compaction is probably mediated by adhesion glycoproteins.
Morula
- The zygote reaches the morula stage around day 3 of development, when it is comprised of between 16 and 32 cells.
- Morula means mulberry, which is what the cell mass resembles. Roll over the image to see the labels and outlines of blastomeres.
- The cells of the morula become segregated into inner and outer cell masses that will eventually become hollow forming the blastocyst.
Fig 3. The morula consists of between 16 and 32 cells, contained in the zona pellucida. The cells are compacted to accommodate to the space constrained by zona pellucida.
Blastocyst
Accumulation of fluid within the morula, converts it into fluid filled blastocyst. At this time, some of the cells aggregate at one pole of the blastocyst, forming the inner cell mass and which are committed to forming the embryo proper.
The cells in the perimeter of the blastocyst form the walls of the blastocoel to contain the fluid, that accumulates in the blastocyst. They make up the outer cell mass and are committed for forming the supportive membranes necessary for development to proceed normally.
Fig 5.. Models of the blastocyst. Roll over the image and see that the inner cell mass (embryoblast) and the outer cell mass (trophoblast can be seen.
Fig 4. The morula becomes a hollow ball of cells known as the blastocyst, with a blastocele cavity and an inner cell mass committed to form the embryo.
While it is still contained within the zona pellucida, the blastocyst is at a point where it needs to attach to the uterine mucosa and implant for development to continue.
It is likely that the hydrostatic pressure generated by the accumulation of fluid in the blastocoel cavity of the blastocyst facilitates rupture of the zona pellucida, allowing the blastocyst to 'hatch"
K. Hardy (2012) CIL:39006, Homo sapiens, embryonic cell. CIL. Dataset. Attribution. CC BY NC ND license.
Fig 6. Blastocyst 'hatching' from zona pellucida.
Fig 3. Hatched blastocyst, free to attach to the uterine mucosa and begin invasion into the endometrium
The blastocyst is divided into an inner cell mass or embryoblast which will form the tissues of the embryo, and an outer cell mass or trophoblast that will contribute to production of the fetal membranes to provide physical and nutritional support for the embryo and fetus.
Once freed from the confines of zona pellucida, the blastocyst attaches to the endometrium of the uterine mucosa and begins to implant into the uterine wall for gestation.
The syncytiotrophoblast produces enzymes to erode the endometrial tissue, while consuming decimal cells as a source of sustenance.
In a journey of one week's duration, the single cell zygote is transformed into a complex aggregate of two populations of cells committed to the singular task of building an embryo. It reaches the lumen of the uterus. Soon the greater complexity of structure will require a more sophisticated method of providing structural and nutritional support. Implantation into the uterine mucosa is necessary to establish the placenta and supporting membranes needed for gestation. During pregnancy, the embryo and fetus enjoy a parasitic relationship with their host, the mother.
Fig 3. The morula consists of between 16 and 32 cells, contained in the zone pellucid.
The presence of tight junctions between cells forming the outer cell mass (trophoblast) serve to isolate the blastocyst from rejection by the maternal immune system as this foreign body invades into the endometrium.
Cells forming the inner cell mass (embryoblast) have gap junctions to facilitate intercellular communication.
Implantation
The innermost layer of the uterine wall, stratum functionalis of the endometrium, is in the progestational or secretory phase of the menstrual cycle.
At the end of the week one the "hatched" blastocyst is free in the uterine cavity and begins implantation, by attaching to and eroding into the uterine wall.
Under the influence of progesterone, from the corpus luteum, the stratum functionalis has become thick and glandular, secreting a glycogen rich material to nourish the blastocyst as it implants, a process that is generally completed by the end of week 2. As it erodes deeper into the endometrium, it also cannibalizes decidual cells as an additional source of sustenance.
Once free from the zone pellucida, the blastocyst attaches to the endometrium of the uterus and begins to invade the uterine lining.
Day 09
A mucus plug seals the defect in the endometrium where the blastocyst invaded. Spaces begin to develop in the synciotrophoblast. These are called trophoblastic lacunae.
The cells of the trophoblast differentiate into two layers, cytotrophoblast and syncytiotrophoblast.
Syncytiotrophoblast develops by fusion of daughter cells generated by mitosis in the cytotrophoblast.
The image on the left depicts implantation of the blastocyst into the stratum functionalis. The leading edge of the invasion is carried out by the syncytiotrophoblast, which produces the necessary enzymes to erode into the uterine wall.
Apoptosis of endometrial stromal cells facilitates the process of implantation. Some stromal cells near the implantation site assume a polyhedral shape and accumulate lipids and glycogen to become decidual cells.
The syncytiotrophoblast cannibalizes these cells, providing nutritional support for the invading blastocyst.