Early Embryology. GEMP – 2006 Avinash Bharadwaj. Gross Form, Correlation. Embryology. Cellular and Molecular phenomena. Errors in development Structural Molecular (Clinical aspects). Evolutionary mirror. Why and How. Sexual Reproduction. Vast potential for variation
GEMP – 2006
TestisMale Reproductive System
VaginaFemale Reproductive System
VaginaFemale Reproductive System
The chromosomes have replicated prior to division, but not yet seen as discrete structures.
The nuclear envelope is intact.
In each pair, there is one maternal chromosome and one paternal.
A chromosome, when fully condensed may be shown as in ‘A’. It has two identical halves called chromatids, shown at ‘B’. The most important point to be understood here is that each chromosome has replicated.
A chromosome in a non-dividing cell is a chromatid, if at all we could see it!
Only two chromosome pairs are shown in the nucleus in these pictures. One pair is shown in pink, one in blue. They are still being condensed.
During metaphase, the chromosomes are arranged along a plane in the middle of the cell (‘equatorial plane’).
A ‘spindle’ of microtubules (mitotic spindle) attaches the chromosomes to the centrosomes. Shortening of the microtubules separates the chromatids. The chromatids (chromosomes of the daughter cells) migrate towards the poles of the dividing cell.
The cytoplasm divides to create two roughly equal cells. Note how the chromosomes ‘disappear’.
The picture at top left shows the cell resting after the replication of chromosomes.
Once again we see two representative pairs of chromosomes (bottom). In each pair, paternal and maternal chromosomes are shown in different colours.
Meiosis is a two-stage division. The two stages are often called meiosis I and meiosis II. We are looking at meiosis I.
Homologous chromosomes are arranged next to each other lengthwise. Their corresponding arms cross at a number of points. These points of crossing are called chiasmata.
At these points of crossing, homologous chromosomes exchange segments.
When this exchange is complete, the two homologous chromosomes cease to be what they were. Each one has segments from both parental chromosomes.
The possibilities of chiasmata formation are virtually unlimited. Every cell undergoing meiosis therefore, can give rise to a unique combination of resultant chromosomes.
Separation of chromosomes now follows a different pattern.
Chromatids do NOT separate. One entire replicated chromosome from each pair moves to one pole of the cell.
At the end of meiosis I, the two resultant cells are thus haploid, containing one member from each pair.
It is worth repeating that the chromosomes of these cells are NOT identical with those of any of the parents. Each of these cells has genes coming from both parents.
Considering that the same process has been followed in every meiotic division in the parents of this individual, there has been a great mixing of grandparental genes as well!
The cells begin the second division soon, without an S phase.
Recall that each of these cells is haploid and the chromosomes are replicated.
In meiosis II, the chromatids of these chromosomes separate.
On the right, we see the beginning of the formation of four cells.
At the end of meiosis therefore, four unique, haploid cells are formed.
In the male, spermatogenic activity begins at puberty.
The spermatogenic cells, called spermatogonia undergo mitotic division, whereby some cells remain as spermatogonia and some take the path of meiosis.
Each meiotic division produces four haploid cells called spermatids. Spermatids then undergo structural changes – loss of some cytoplasm, formation of a tail.
Spermatogenesis is a continuous process.
The average duration of the cycle of changes is 28 days, though cycles as short as 20 days or as long as 35 days are normal. In the average 28-day cycle, ovulation takes place around day 14.
If the oöcyte is not fertilised, most of the endometrium is discarded. This is accompanied by a significant amount of blood loss through the broken blood vessels. The endometrial tissue with the blood constitutes menstrual flow which lasts 3 to 5 days.
Menstrual flow is the only reliable external marker of the cyclic changes. The first day of the flow is thus taken as “Day 1” of the cycle, though this in fact marks the end of the previous cycle.
It is noteworthy that the interval between ovulation and the next menstrual period is rather constant around 14 days, whereas that between day 1 and ovulation varies according to the length of the cycle in a paticular individual.
At the tip of the sperm head is an enzyme-containing structure called acrosome.
Acrosomal enzymes allow the sperm to ‘bore’ through the zona pellucida.
The entry of one sperm causes a molecular reaction in the zona pellucida which prevents the entry of any other sperm.
The entry of the sperm is also followed by the completion of the second meiotic division and a second polar body is formed.
The ovum now has two ‘pronuclei’ male and female. These soon lose their nuclear membranes and a diploid cell is formed, called the zygote.
These events are shown in the next slide where the polar bodies are also shown.
EImplantation and beyond…
The terms epiblast and hypoblast are introduced here to make the description cohesive and complete. The concepts introduced in the next slide are more important.
Sectioned along this line
Primitive streakTrilaminar Embryo
In surface view, the embryo appears as a flat disc with the future head and tail ends established. At the tail end, cells of the epiblast begin to migrate as indicated by the curved arrows in the sectional view below. The site of this migration is seen as the ‘primitive streak’. This migration establishes the final three layers of the embryo – ectoderm, mesoderm and endoderm (entoderm).
The core concepts here are :
1. From the inner cell mass, a trilaminar embryo emerges.
2. The amnion is continuos with the ectoderm and encloses the amniotic cavity.
The hypoblast is replaced by the endoderm and the yolk sac also changes its nature. However, you may overlook this detail!
EntodermNotochord & Neural Tube
Continuing with the sectional view in the last slide…
In the upper figure observe the three germ layers the colours of their labels match their representations. The mesoderm is unlabelled.
In the centre is a cordlike structure, the notochord (*) that runs length wise through the embryo. This is the notochord – it is the ‘axis’ of bilateral symmetry of the embryo.
In the middle figure a groove (blue arrow) formed by a specialised area (between the red lines) of the ectoderm is shown. This grove is the forerunner of the nervous system. The lips of this groove approximate to form a tube, the neural tube. The lips of this groove (arrows in the third figure) form the neural crest. Soon, the neural crest and tube will be internalised with the rest of the ectoderm becoming a continuous layer over it.
Changes are taking place in the mesoderm as well, these are described next.
EntDivisions of Mesoderm
A huge bulk of body tissues arises from the mesoderm. These are listed a little later.
The salient feature illustrated here is the division of this layer into three parts. The notochord is indicated by the black arrow.
Just next to the notochord (the axis!) is a mass of mesoderm called paraxial mesoderm (blue arrow). This is a somewhat cylindrical mass stretching along the length of the embryo.
On the extreme lateral side is a plate-like mass, the lateral plate mesoderm.
The not-so-well-defined mass in between the two is the intermediate mesoderm.
The lateral plate mesoderm shows a clear split enclosing a cavity (x). This is the forerunner of a great system of cavities in the body, the coelom. This will be described much later. At this stage just note that one ‘wall’ of the coelom faces the ectoderm, the other faces the endoderm.
We are not just symmetrical, we are ‘sliced’ too! The ‘slices of the body are ‘segments’. Though the entire body has a segmental pattern, in the fully formed human there is no outward sign of this. In the embryo, the segmentation is best seen in the paraxial mesoderm.
You can see the blocks of tissue on the left and right sides of the central line of the body in the upper picture. These are segments of the paraxial mesoderm. They are called somites.
Each somite further differentiates into a sclerotome and a dermomyotome. The root ‘tome’ indicates a cut or a slice, sclero- is hard. A sclerotome gives rise to a mass of bone. Most of the sclerotomes form parts of vertebrae (more later!)
Derm- indicates a part of the skin, here it specifically indicates dermis, the connective tissue component of the skin. Myo- indicates muscle.
From this it should be clear that each somite gives rise to bone, muscle and dermis of a segment of the body. This concept will of great help in our understanding of the anatomy of the vertebral column, nerves and skeletal muscles of the body.
The ectoderm gives rise to the covering of the body – specifically, the epidermis (not skin!), hair, nails, the epithelium that covers the eye and the glands in the skin.
The mesoderm produces almost all muscle and all connective tissue. Needless to say, the body cavities formed by the split of lateral plate mesoderm are lined by epithelium which is also of mesodermal origin. Blood vessels and the cavity of the heart also arise from the mesoderm and their lining epithelium is mesodermal in origin. Parts of the urogenital system develop from the mesoderm as well.
It is pertinent to note here that almost all skeletal muscle comes from somites (special cases will be mentioned later!). The urogenital system has parts which originate from the intermediate mesoderm.
Note that this listing aims to give a comprehensive description, some of these points will be reinforced when we deal with the development of individual systems.
The endoderm, like the ectoderm, has limited derivatives – it forms the lining epithelium of the digestive system and its glands.
How does the flat entodermal layer give rise to the tubular digestive system…?
4Head, Tail and Lateral Folds
In the pictures below, the mesoderm is not shown. These are sagittal sections of the embryo. The ectoderm is blue, entoderm yellow.
In the first picture, the head end is indicated by the red (cardiogenic) area that will form the heart.
The entire thickness of the embryo begins forms folds at the head and the tail ends. In successive pictures, observe how the endoderm forms a tube, the yolk sac communicates with this tube via a progressively narrowing structure and how the heart ‘descends’ to its final position.
In the transverse section, similar lateral folds complete the formation of the embryo that resembles the three dimensional human being.
Further details are described with the development of individual systems.
A key event of great concern from the mother’s point of view is the time and site of implantation. Though we have considered ovulation as the starting point of the story, subsequent events are more accurately timed as after fertilisation.
When the conceptus reaches the blastocyst stage, the zona pellucida disappears and the invasive activity of the trophoblast begins. If this happens before the embryo reaches the uterus, implantation occurs in the tube. The tube is not equipped to handle the growing embryo. Implantation in the tube therefore invariably causes rupture of the tube or the death of the embryo. In the latter case the dead embryo is simply aborted, but the rupture of the tube is a potential emergency.
In rare cases implantation may occur on the surface of the ovary or even in the peritoneal cavity (the oöcyte is released in the peritoneal cavity whence it is picked up by the fimbriae of the tube). In exceptional cases a peritoneal implantation may even reach full term.
The commonest (and the ideal) site of implantation is the fundus or the upper part of the body of the uterus. In this case the trophoblast forms a placenta which is attached to the same part of the uterus.
Too late an implantation may occur in the lower part of the uterus, in which case the placenta may be placed across the inner opening of the cervix. Distention of the uterus in the later part of pregnancy may cause premature separation of the placenta with bleeding that threatens both the foetus and the mother.
The total period of intrauterine development can be divided into three parts.
The developing human truly begins its life at the moment of fertilisation. However, this event cannot be recognised clinically. Ovulation is another landmark, but has the same drawback, though there are methods with a fair degree of accuracy. The only event that has an external manifestation is menstruation.
As we proceed through further system blocks, we shall deal with further development of individual systems. It is interesting to note that even during development, the functionality of some systems (CVS) is essential for maintaining the embryo / foetus, some systems (CNS, Kidneys) show physiological activity which is essential to a variable degree and some become functional only at birth (respiratory). The degree of differentiation and specialisation involves acquisition of specific histological features (histogenesis) and in the case some organs (lungs, bones) histological development is carried well into postnatal life.
Much as we shall focus on the ‘embryonic period’, clinically the foetal period is of considerable importance. Similarly, in our current discussion we have but mentioned aspects of trophoblastic specialisation (placenta). Full details of these aspects are beyond the scope of the current discussion.
Not too long ago embryology was also called ‘developmental anatomy’. This science has now breached barriers between disciplines and progressed into the realm of molecular biology and genetics. Well, for the moment we have to draw a line and wait for the exciting aspects of human development!