Human Embryology PDF

Chapter Some Preliminary Considerations HIGHLIGHTS cells resulting from a mitotic division are similar to the parent cell, and have the same...

Chapter Some Preliminary Considerations HIGHLIGHTS cells resulting from a mitotic division are similar to the parent cell, and have the same Embryology is the study of the development number of chromosomes (46). of an individual before birth. A special kind of cell division takes place in D u r i n g the first t w o m o n t h s we call the the testis and ovary for formation of gametes. developing individual an embryo. After that It is called meiosis. The gametes resulting from we call it a fetus. meiosis have t h e h a p l o i d n u m b e r of chromosomes (23). The various gametes The testis is the male sex organ or male gonad. formed do not have the same genetic content. The ovary is the female sex organ or female gonad. They produce gametes. Male gametes produced by the testis are called spermatozoa. The process is called spermato- genesis. Female gametes produced by the ovary are called ova. The process is called oogenesis. Spermatogenesis and oogenesis are together called gametogenesis. Fertilization t a k e s place w h e n one WHAT IS EMBRYOLOGY? spermatozoon enters an ovum. The fused ovum and sperm form the zygote. Every individual spends the first nine months (266 C h a r a c t e r s of p a r e n t s are t r a n s m i t t e d to days or 38 weeks to be exact) of its life within the offspring through codes borne on strands of w o m b (uterus) of its mother. During this period it DNA. Genes are made of such strands of DNA. develops from a small one-celled structure to an They are located on chromosomes. organism having billions of cells. Numerous tissues and organs are formed and come to function in A typical cell c o n t a i n s 46 c h r o m o s o m e s perfect harmony. The most spectacular of these (= diploid number). changes occur in the first two months; the unborn A gamete contains 23 chromosomes {= haploid baby acquires its main organs and just begins to number). be recognizable as h u m a n. D u r i n g these t w o The diploid number of chromosomes is restored m o n t h s we call the developing individual an as a result of fertilization. embryo. From the third month until birth we call it a fetus. Multiplication of cells takes place by cell division. The usual method of cell division, Embryology is the study of the formation and seen in most tissues, is called mitosis. Daughter development of the embryo (or fetus) from the  Human Embryology moment of its inception up to the time when it is is referred to as the diploid (or double) number. born as an infant. However, in spermatozoa and ova the number of chromosomes is only half the diploid number, i.e. twenty-three. This is called the haploid (or half) Why a Medical Student should number. After fertilization the resulting zygote has Study Embryology? twenty-three chromosomes from the sperm (or 1. This subject tells us h o w a single cell (the father), a n d t w e n t y - t h r e e from the o v u m (or fertilized ovum) develops into a newborn, mother). The diploid number is thus restored. containing numerous tissues and organs. 2. This knowledge helps us understand many Autosomes and Sex Chromosomes complicated facts of adult anatomy. 3. Embryology helps us understand why some The forty-six chromosomes in each cell can be children are born with o r g a n s t h a t are divided into forty-four autosomes and two sex abnormal. Appreciation of the factors res- chromosomes. T h e sex chromosomes may be of ponsible for maldevelopment assists us in two kinds, X or Y. In a man there are forty-four preventing, or treating such abnormalities. autosomes, one X-chromosome and one Y-chromosome; while in a woman there are forty- four autosomes and two X-chromosomes in each Gonads and Gametes cell (Fig. 1.1). When we study the forty-four The cells that carry out the special function of autosomes we find that they in fact consist of reproduction are called gametes. The development twenty-two pairs, the two chromosomes forming of a new individual begins when one male gamete a pair being exactly alike {homologous {sperm or spermatozoon) meets and fuses with one chromosomes). In a w o m a n the two female gamete (ovum or oocyte). The process of X-chromosutnes form another such pair; in a man fusion of male a n d female g a m e t e s is called this pair is r e p r e s e n t e d by o n e X- a n d o n e fertilization. The fused ovum and spermatozoon Y-chromosome. One chromosome of each pair is form the zygote. The zygote later develops into derived from the mother and the other from the an embryo and then into a fetus. father. The male sex cells (spermatozoa) are produced in the male gonads (testes) while the female sex Chromosome Structure cells (ova) a r e p r o d u c e d in female g o n a d s In a resting cell, chromosomes are not visible under (ovaries). The formation of spermatozoa in the a light microscope as their chromatin material is testis is called spermatogenesis while the formation highly dispersed. However, during cell division of ova in the ovary is called oogenesis. The t w o the chromatin network in the nucleus becomes are collectively referred to as gametogenesis. condensed into a number of chromosomes. The To understand the structure of gametes and to appearance of a typical chromosome is illustrated study how they are formed, it is necessary to first in Fig. 1.2. It is made up of t w o rod-shaped review some facts regarding chromosomes and cell structures or chromatids placed m o r e or less division. parallel to each other. The chromatids are united to each other at a light staining area called the SOME FACTS ABOUT CHROMOSOMES centromere (or kinetochore). Each chromatid has two arms, one on either side of the centromere. Haploid and Diploid Chromosomes Individual chromosomes differ from one another The number of chromosomes in each cell is fixed in total length, in the relative length of the two for a given species and in man it is forty-six. This arms and in various other characteristics; these  Some Preliminary Considerations MAN WOMAN Fig. 1.1 Number of chromosomes in the somatic cells of a man and of a w o m a n. Significance of Chromosomes Satellite. The entire human body develops from the fertilized 11 Secondary constriction"*" ovum. It is, therefore, obvious that the fertilized Short arm ovum contains all the information necessary for of chromatid formation of the numerous tissues and organs of Centromere—* the body, and for their orderly assembly and function. Each cell of the body inherits from the \ fertilized ovum, all the directions that are necessary Long arm \ for it to carry out its functions throughout life. of chromatid ' This tremendous volume of information is stored within the chromosomes of each cell. J u Each c h r o m o s o m e bears on itself a very large number of structures called genes. Genes are made up of a nucleic acid called Fig. 1.2 Diagram to show the parts of a typical deoxyribonucleic acid (or DNA) and all chromosome. information is stored in the molecules of this substance. differences enable us to identify each chromosome Genes are involved in synthesis of proteins. individually. Classification of chromosomes in this Proteins are the most important constituents way is called karyotyping. Karyotyping makes of our body. They make up the greater part it possible for us t o detect a b n o r m a l i t i e s in of each cell and of intercellular substances. c h r o m o s o m e number or in individual chromo- Enzymes, hormones and antibodies are also somes. proteins.  Human Embryology The nature and functions of a cell depend MITOSIS o n the p r o t e i n s synthesized by it. It is, therefore, not surprising that one cell differs M a n y cells of the body have a limited span of from another because of the differences in functional activity, at t h e end of which they the proteins that constitute it. undergo division into t w o d a u g h t e r cells. The daughter cells in turn have their o w n span of We n o w k n o w t h a t g e n e s c o n t r o l t h e activity, followed by another division. The period d e v e l o p m e n t a n d f u n c t i o n i n g of c e l l s , by during which the cell is actively dividing is the d e t e r m i n i n g w h a t t y p e s of p r o t e i n s will be p h a s e of m i t o s i s. T h e p e r i o d b e t w e e n t w o synthesized within t h e m. T h u s genes play an successive divisions is called the interphase. important role in the development of tissues and Mitosis is conventionally divided into a number organs of an individual. of stages called prophase, metaphase, anaphase T r a i t s ( c h a r a c t e r s ) of a n i n d i v i d u a l a r e a n d telophase. T h e sequence of events of the d e t e r m i n e d by genes carried on his (or her) mitotic cycle is best understood starting with a chromosomes. As we have seen half of these are cell in telophase. At this stage each chromosome inherited from the father and half from mother. consists of a single chromatid (Fig. 1.3G). With the progress of telophase, the chromatin of the CELL DIVISION c h r o m o s o m e uncoils a n d e l o n g a t e s a n d the c h r o m o s o m e can no longer be identified as Multiplication of cells takes place by division of s u c h. H o w e v e r , it is b e l i e v e d t o r e t a i n its pre-existing cells. Such multiplication constitutes identity during the interphase (which follows an essential feature of embryonic development. telophase). This is shown diagrammatically in Cell multiplication is equally necessary after the Fig. 1.3 A. b i r t h of the i n d i v i d u a l for g r o w t h a n d for During a specific period of the interphase, the replacement of dead cells. We have seen that DNA content of the chromosome is duplicated so c h r o m o s o m e s within the nuclei of cells carry- that another chromatid identical to the original genetic information that controls the development one is formed; the chromosome is n o w made up and functioning of various cells and tissues; and, of two chromatids (Fig. I.3B). When mitosis begins therefore, of the body as a whole. When a cell (i.e. d u r i n g p r o p h a s e ) the c h r o m a t i n of the divides it is essential t h a t the entire genetic chromosome becomes gradually more and more information within it be passed on to both the c o i l e d so t h a t t h e c h r o m o s o m e b e c o m e s daughter cells resulting from the division. In other r e c o g n i z a b l e as a t h r e a d - l i k e s t r u c t u r e t h a t words, the daughter cells must have chromosomes gradually acquires a rod-like appearance identical in number (and in genetic content) to (Fig. 1.3C). Towards the end of prophase, the two those in the mother cell. This type of cell division c h r o m a t i d s c o n s t i t u t i n g the c h r o m o s o m e is called mitosis. become distinct (Fig. 1.3D) and the chromosome A different kind of cell division called meiosis n o w has the typical s t r u c t u r e i l l u s t r a t e d in occurs during the formation of the gametes. This Fig. 1.2. consists of two successive divisions called the first W h i l e t h e s e c h a n g e s a r e o c c u r r i n g in and second meiotic divisions. The cells resulting chromosomes, a number of other events are also from these divisions (i.e. gametes) differ from other taking place. T h e t w o centrioles separate and cells of the b o d y in t h a t (a) the n u m b e r of move to opposite poles of the cell. They produce c h r o m o s o m e s is reduced to half the n o r m a l a n u m b e r of microtubules that pass from one number, and (b) the genetic information in the c e n t r i o l e to t h e o t h e r a n d form a spindle. various gametes produced is not identical. Meanwhile the nuclear membrane breaks down  Some Preliminary Considerations LATE INTERPHASE DNAof each chromosome has under- gone duplication. Fig. 1.3 Scheme to show the main stages of mitosis. and nucleoli d i s a p p e a r (Fig. 1.3D). W i t h the longitudinally into two so that the chromatids now formation of the spindle, chromosomes move to a become independent chromosomes. position midway between the two centrioles (i.e. At this stage the cell can be said to contain at the equator of the cell) where each chromosome forty-six pairs of chromosomes. One chromosome becomes attached to microtubules of the spindle of each such pair now moves along the spindle to by its centromere. This stage is referred to as cither pole of the cell (Fig. 1.3F). This is followed metaphase (Fig. 1.3E). In the anaphase the by telophase in which the two daughter nuclei are c e n t r o m e r e of e a c h c h r o m o s o m e s p l i t s formed by appearance of nuclear m e m b r a n e s.  Human Embryology C h r o m o s o m e s gradually elongate and become indistinct. Nucleoli reappear. T h e centriole is duplicated at this stage or in early interphase 1. Chromosomes become visible. Each (Fig. 1.3G). chromosome is made The division of the nucleus is accompanied by up of two chromatids the division of the cytoplasm. In this process (but these cannot be made out separately). (cytokinesis) the organelles are presumably duplicated and each daughter cell comes to have a full complement of them. MEIOSIS 2. Two homologous As a l r e a d y s t a t e d m e i o s i s c o n s i s t s of t w o chromosomes come successive divisions called the first and second to lie side by side forming a bivalent. meiotic divisions. During the interphase preceding the first division, duplication of the D N A content of chromosomes takes place as in mitosis. As a result, another chromatid identical to the original one is formed. Thus each chromosome is now made up of two chromatids. 3. Four chromatids First Meiotic Division are now distinct and form a tetrad. 1. The prophase of the first meiotic division is prolonged and is usually divided into a number of stages as follows: (a) Leptotene. T h e c h r o m o s o m e s b e c o m e 4. The two 'central' visible (as in m i t o s i s ). A l t h o u g h each chromatids become chromosome consists of two chromatids, coiled on each other so that they cross at these cannot be distinguished at this stage a number of places. (Fig. 1.4A). Only one such crossing (b) Zygotene. We have seen that the forty-six is shown. chromosomes in each cell in fact consist of t w e n t y - t h r e e p a i r s ( t h e X a n d Y chromosomes of a male being taken as a pair). The t w o chromosomes of each pair 5. The chromosomes come to lie parallel to each other, and are now separate. The closely apposed. This pairing of chromo- 'central' chromatids 'break' at the points of somes is also referred to as synapsis or crossing and unite conjugation. The two chromosomes with the opposite together constitute a bivalent (Fig. 1.4B). chromatid. (c) Pachytene. T h e t w o chromatids of each chromosome become distinct. The bivalent Fig. 1.4 Stages in the prophase of the first now has four chromatids in it and is called meiotic division.  Some Preliminary Considerations over. For sake of simplicity only one such crossing is shown in Fig. 1.4D. At the site where the chromatids cross they become iX adherent; the points of adherence are called chiasmata. (d) D i p l o t c n e. T h e t w o c h r o m o s o m e s of a bivalent n o w try to move a p a r t. In the process, the chromatids involved in crossing METAPHASE over 'break' at the points of crossing and The nuclear membrane disappears. Spindle forms the 'loose' pieces become attached to the and chromosomes are attached to it by their o p p o s i t e c h r o m a t i d. T h i s r e s u l t s in centromeres. exchange of genetic material between these chromatids. A study of Fig.l.4E will show that each of the four chromatids of the tetrad now has a distinctive genetic content. 2. This is followed by metaphase. As in mitosis the forty-six chromosomes become attached t o the spindle at the e q u a t o r , the t w o chromosomes of a pair being close to each ANAPHASE other (Fig. 1.5A). One entire chromosome of the pair moves to either 3. The anaphase differs from that in mitosis pole. Note thai the centromeres do not divide. in t h a t there is no splitting of the centromeres. O n e encire c h r o m o s o m e of each pair moves to each pole of the spindle (Fig. 1.5B). The resulting daughter cells, therefore, have twenty-three chromosomes, each made up of two chromatids (Fig. 1.5C). 4. The anaphase is followed by the telophase in which t w o daughter nuclei are formed. TELOPHASE The division of the nucleus is followed by Note that the chromosomes in each cell have been reduced to the haploid number. division of the cytoplasm. Second Meiotic Division Fig. 1.5 Metaphase (A), anaphase (B), and telophase (C) of the first meiotic division. The first meiotic division is followed by a short interphase. This differs from the usual interphase a tetrad. There are t w o central a n d t w o in t h a t there is no duplication of DNA. Such p e r i p h e r a l c h r o m a t i d s , o n e from e a c h duplication is unnecessary as chromosomes of cells c h r o m o s o m e (Fig. 1.4C). An i m p o r t a n t resulting from the first division already possess event n o w takes place. T h e two central two chromatids each (Fig. 1.5C). c h r o m a t i d s (one belonging to each The second meiotic division is similar to mitosis. chromosome of the bivalent) become coiled However, because of the crossing over that has over each other so t h a t they cross at a occurred during the first division, the daughter number of points. This is called crossing cells are not identical in genetic content (Fig. 1.6).  Human Embryology spermatozoa and ova. It is, therefore, not surprising t h a t no t w o persons (except identical twins) are alike. A NOTE ON CHRONOLOGY OF EMBRYOLOGICAL EVENTS In an earlier section it has been emphasized that one of the main objectives of the study of e m b r y o l o g y , by m e d i c a l s t u d e n t s , is t o u n d e r s t a n d t h e c a u s a t i o n of c o n g e n i t a l a n o m a l i e s. In this c o n n e c t i o n it has been observed that if a growing embryo is exposed Fig. 1.6 Daughter cells resulting from the second to c e r t a i n a g e n t s (chemical o r p h y s i c a l ) , meiotic division. These are not alike abnormalities in development can result. Such because of the crossing-over during the first meiotic division. agents are called teratogens. The list of known teratogens keeps increasing. It has also been Significance of Meiosis observed that some particular organs are most sensitive to teratogens when they are passing Why are no two persons alike? through critical phases in their development. T h i s p e r i o d of g r e a t e s t s u s c e p t i b i l i t y t o 1. In this kind ofcell division there is reduction teratogens differs from organ to organ. of the number of chromosomes from diploid to haploid. At the time of fertilization the The importance of having a knowledge of d i p l o i d n u m b e r (46) is r e s t o r e d. T h i s the timing of embryologies I events thus becomes provides consistency of chromosome number obvious. In the early stages of development, from generation to generation. the age of an embryo is reckoned in days. Later, 2. As stated earlier, the forty-six chromosomes when events are less d r a m a t i c , age can be of a cell consist of twenty-three pairs, one expressed in weeks or months. However, the chromosome of each pair being derived from exact age of an embryo is not always known. the mother and one from the father. During An estimate can be made by observing the size the first meiotic division the chromosomes of the embryo (expressed as C.R. length), or derived from the father and those derived some other feature like the number of somites. from the mother are distributed between the In most textbooks of embryology, there are daughter cells entirely at random. numerous references to the timing of embryonic 3. This, along with the phenomenon of crossing events (most commonly in terms of C.R. length}. over, results in thorough shuffling of the The disadvantage of doing so is that it adds yet genetic material so that the cells produced one more complication to the understanding of as a result of various meiotic divisions (i.e. an already intricate subject. Because of this ova or spermatozoa) all have a distinctive r e a s o n r e f e r e n c e s t o t h e t i m e t a b l e of genetic content. development have been kept to the minimum in the main text of this book. However, a 4. A t h i r d step in this process of genetic timetable of events is a d d e d at the end of shuffling takes place at fertilization when chapters wherever relevant. there is a combination of randomly selected