Embryology Notes PDF

Lecture one General embryology The development of a human being begins with "fertilization", the process by which the spermatozoan and oocyte unite to give rise to the new organism in the uterine tube. The main results of fertilization are 1. Restoration of the diploid number of chromosomes...

Lecture one General embryology The development of a human being begins with "fertilization", the process by which the spermatozoan and oocyte unite to give rise to the new organism in the uterine tube. The main results of fertilization are 1. Restoration of the diploid number of chromosomes 2. Determination of the chromosomal sex 3. Initiation of cleavage. By the end of this process the zygote has split into two cells and a series of mitotic divisions ensue. Once these blastomeres divide three or four times the zygote looking more like a mulberry now is called the morula. This stage is reached three days after fertilization and the embryo then gets ready to enter the uterus. The morula now consisting of around 16 cells consists of a group of centrally located cells the " inner cell mass" and the surrounding layer the "outer cell mass" The Inner cell mass will give rise to the embryo proper, while the Outer cell mass forms the trophoblast which later contributes to the placenta Around day four the morula enters the uterine cavity and fluid begins to penetrate through the zona pellucida (outer lining of the zygote)into the intercellular spaces, gradually these spaces become confluent and then form a single cavity the blastocoele. At this time the embryo is known as the blastocyst. The embryoblast is now located at one pole and the trophoblast cells flatten and form the epithelial wall of the blastocyst. The zona pellucida has now disappeared at what we call the late blastocyst phase and implantation is now possible. Around day six the human trophoblast cells that are just above the embryoblast pole begin to penetrate between the epithelial cells of the uterine mucosa. This penetration is probably caused by mutual interaction between the trophoblast which produces proteolytic enzymes and the endometrium which promotes the proteolytic action of the blastocyst. So by the end of the first week implantation has begun in the uterine mucosa. Fig. 3 - Implantation: 6th –7th day Fig. 4 - Implantation: 7th –8th day 1 Epithelium of the uterine 5 Epiblast endometrium 6 Blastocyst cavity 2 Hypoblast 3 Syncytiotrophoblast (ST) 4 Cytotrophoblast (CT) Second week of development (bilaminar germ disc): On day eight the blastocyst is partially embedded into the endometrial stroma. The trophoblast portion that is over the embryoblast differentiates into two layers : 1. The inner layer of mononucleated cells the "cytotrophoblast" 2. The outer layer of multinucleated zone without distinct cell boundaries the "syncitiotrophoblast" The cells of the embryoblast (the inner cell mass) also differentiate into two germ layers 1. A layer of small cuboidal cells adjacent to the blastocyst cavity the hypoblast 2. A layer of high columnar cells adjacent to the amniotic cavity, the epiblast The cells of each germ layer form a flat disc and together they are known as the bilaminar germ disc. 1 Extraembryonic mesoderm 2 Amniotic cavity 3 Primary yolk sac At this time a small cavity appears within the epiblast, this cavity enlarges to become the amniotic cavity. The epiblast cells adjacent to the cytotrophoblast are called amnioblasts,and together with the rest of the epiblast line the amniotic cavity. By day nine and at the hypoblast end of the disc; flattened cells originating from the hypoblast form a thin membrane known as Heuser's membrane or the exocoelomic membrane. This membrane lines the inner surface of the cytotrophoblast and together with the hypoblast form the lining of the exocoelomic cavity (primitive yolk sac). By the eleventh and twelfth day of devolopment the blastocyst is completely embedded in the endometrial stroma. The yolk sac cells form the extraembryonic mesoderm inside which cavities arise(extraembryonic coeloms). These cavities divide the extraembryonic mesoderm into 1. Splanchnopleuric (facing the exocoelomic membrane) 2. Somatopleuric (facing the cytotrophoblast).this is later called the chorionic plate. On day thirteen, some hypoblast cells migrate along the inside of the exocoelomic membrane forming a secondary yolk sac this is much smaller than the primary yolk sac and during it's formation portions of the primary yolk sac are pinched off and remain as exocoelomic cyst 1. Secondary yolk sac, 2. Excoelomic cyst,3. Amniotic cacity,4.extra embryonic coelom 5.epiblast,6. Connecting stalk,7.hypoblast,10,extraembryonic somatic mesoderm,11.extraembryonic splanchnic mesoderm Third week of development (trilaminar germ disc): The most characteristic event occurring during the third week is gastrulation; the process by which all three germ layers are established. Gastrulation begins with the formation of the primitive streak on the surface of the epiblast.this streak becomes more visible by day sixteen and bulges on either side are noted. The cephalic or rostral end of the streak is known as the primitive node.Cells of the epiblast migrate in the direction of the primitive streak to form the intraembryonic mesoderm and intraembryonic endoderm. Fig. 2 - Dorsal view of the embryonic disk 1 Primitive groove 2 Primitive pit 3 Primitive node 4 Oropharyngeal membrane 5 Cardial plate 6 Sectional edge of amniotic membrane 7 Mesoderm 8 Endoderm 9 NB Future cloacal membrane 1+2+3 primitive streak Once the epiblast cells reach the streak the start to detach and slip underneath it. Once the cells have invaginated; some displace the hypoblast and form endoderm, and others lie between the epiblast and the endoderm and form the mesoderm. Cells remaining in the epiblast then form the ectoderm.  Fig. 4 - Transverse section at the level of the primitive groove 1 Primitive groove 2 Epiblast 3 Extraembryonic mesoderm 4 Definitive endoderm 5 Invading epiblastic cells forming the intraembryonic mesoderm 6 Hypoblast Thus the epiblast during gastrulation is the source of three germ layers. As more cells move between the epiblast and the hypoblast they begin to spread in lateral and cephalic directions,gradually they migrate beyond the margin of the disc and establish contact with the extraembryonic mesoderm covering the yolk sac and amnion. In the cephalic direction they pass on each side of the prochordal plate to meet each other in front of it. Here is where they form the cardiogenic plate. 11. prochordal plate Another interesting process occurring in this week is formation of the notochord: Cells invaginating the primitive pit move forward in the cephalic direction until they reach the prochordal plate here they loop and form the notochordal process tube like process where the central canal is considered an extension of the primitive pit. By day seventeen,the mesodermal layer and notochordal process separate the ectoderm and endoderm except at 1. The prochordal plate in the cephalic direction 2. The cloacal membrane in the caudal direction In these two positions ectoderm and endoderm are tightly adherent. By day eighteen the floor of the notochordal process fuses with the underlying endoderm and disintegrates. The upper part thickens and lumen disappears. when the proper chord forms the notochord cells again detach from the endoderm which in turn uninterruptedly covers the roof of the yolk sac. Neurulation is one more process beginning in the third week. With the appearance of the notochord and under its inductive influence; the ectoderm overlying the notochord thickens to form the neural plate. Cells of this plate make up the neuro ectoderm and their induction represents the initial event of neurulation. The neural plates edges then elevate and form neural folds, while the depressed mid-region forms a groove the neural groove. The neural folds meet at the level of the fourth somite (mesoderm derivative also forming in week three) and close to form the neural tube. Formation of the neural tube 1. Notochord 2. Neural crest 3. Neural fold 4. Surface ectoderm Formation of the neural tube 1. Notochord 2. Neural crest 3. Neural fold 4. Surface ectoderm Formation of the neural tube 1. Notochord 2. Intermediate zone of neural crest 3. Neural tube 4. Surface ectoderm  1. Notochord 2. Dorsal root ganglion 3. Neural tube 4. Surface ectoderm Formation of the neural tube Human embryo - day 19 1. Neural plate 2. Primitive node 3. Primitive streak 4. Cut edge of amnion Human embryo - day 20 1. Neural fold 2. Primitive node 3. Primitive streak 4. Somite 5. Neural groove 6. Cut edge of amnion  1. Anterior neuropore 3. Posterior neuropore 4. Somite Human embryo - day 23 Weeks three to eight (embryonic Period) Along with the previously mentioned event s growth continues and the neural tube at the caudal and cephalad ends of the embryo remains temporarily in open connection with the amniotic cavity by the posterior and anterior neuropores respectively. Closure of the anterior neuropore occurs approximately day 25,where the posterior neuropore closes at day 27. Neurulation is then complete and the central nervous system is represented by a closed tubular structure with a narrow caudal portion the spinal cord and a much broader cephalic portion characterize by a number of dilatations,the brain vesicles. As the neural folds elevate and fuse, cells at the lateral border or crest of the neuroectoderm begin to dissociate from their neighbours , these are known as the neural crest cells. These cells will undergo an epithelial to mesenchymal transition as it leaves the neuroectoderm by active migration and displacement to enter the underlying mesoderm. By the time the neural tube is closed, two other ectodermal thickenings are visible in the cephalic region, the otic placode and the lens placode. During development, the otic placode invaginates and forms the otic vesicle which develops into the structures needed for hearing and equilibrium. The lens placode also invaginates during the fifth week and forms the lens. As for the mesoderm layer it's cells form a thin sheet of loosely woven tissue on each side of the midline. By about day seventeen the cells close to the midline proliferate and form a thickened plate of tissue the " paraxial mesoderm". More laterally the mesoderm layer remains thin and is known as the lateral plate. Intercellular cavities form and coalesce in this layer and divide the plate in to 1. A layer continuous with the mesoderm covering the amnion (somatic or parietal mesoderm) 2. A layer continuous with mesoderm covering the yolk sac (splanchnic or visceral mesoderm) Together these layers line the newly formed cavity the intraembryonic coelomic cavity which in each side is continuous with the extraembryonic coelom. The tissue connecting the paraxial mesoderm to the lateral plate is called the intermediate mesoderm. By the beginning of the third week paraxial mesoderm becomes organized into segments(somitomeres). These appear first in the cephalic region of the embryo and their formation proceeds in the cephalocaudal direction. In the head region these structures in association with the segmentation of the neural plate form neuromeres and contribute the majority of head mesenchyme. From the occipital region caudally somitomeres become further organized into somites. The first pair of somites arises in the cervical region approximately at the twentieth day of development. From here three somites arise per day until at the end of week five 42-44 pairs arepresent. The are 4 occipital , 8 cervical, 12 thoracic,5 lumbar , 5 sacral and 8-10 coccygeal pairs. The first occipital and 5-7 coccygeal somites later disappear while the rest form the axial skeleton. Diiferentiation of the somite begins around week four. Cells forming the ventral and medial walls of the somites lose their compact organization and become polymorphous and shift their position to surround the notochord. These cells now known as the sclerotome form a loosely woven tissue known as mesenchyme. They surround the spinal cord and notochord to form the vertebral column. The remaining dorsal somite wall, now referred to as the dermomyotome , gives rise to a new layer of cells the myotome. Each myotome provides musculature for its own segment. After the cells of the dermomyotome have formed the myotome ,they lose their epithilial characteristics( becoming the dermatome and spread under the overlying ectoderm ,here they form the dermis and subcutaneous tissue of the skin hence each somite forms its own sclerotome and its own myotome and dermatome. Each myotome will have its own segmental nerve component. The intermediate mesoderm differentiates entirely different to the somites.it later develops in to the excretory units of urinary system. The parietal and visceral mesoderms line the intraembryonic coelom. The parietal mesoderm together with the overlying ectoderm will form the lateral and ventral body walls. The visceral mesoderm together with the embryonic endoderm will form the gut wall. The cells facing the coelomic cavity will form thin serous membranes which will line the peritoneal,pleural and pericardial cavities. Also at the beginning of the third week mesoderm cells located in the visceral mesoderm of the yolk sac differentiate into blood cells and blood vessels. These vessels will gradually establish contact with the extraembryonic vessels thus connecting the embryo to the placenta. The gastrointestinal tract is the main organ system derived from the endodermal germ layer. its formation is greatly dependant on the cephalocaudal (due to growth of the CNS )and lateral folding of the embryo(produced by the growing somites). This is a passive event and consists of inversion and incorporation of part of the endoderm lined yolk sac into the body cavity. At the end of this period the main organ systems have been established, and the major features of the embryo are recognizable by the end of the second month. Foetal period week 9-birth: This period is characterized by the rapid growth of the body and maturation of the organ systems. Growth in length is particulary striking during the 3rd 4th and 5th months. Another striking change is the slowdown in head growth. As the foetus grows the head grows proportionately less than the rest of the body hence what was once the largest structure in the embryonic period is only a quarter of the crown heel length at birth. Germ layer Derivatives Ectoderm ( Neural Crest) - Spinal and autonomic ganglia - Ganglia of v, vii ,ix,x - Adrenal medulla - Ectomesenchyme - Bones & skull - Dentin, periodontal ligament - Melanocytes ( Surface ectoderm) - Epidermis, hair, nails - Cutaneous glands - Anterior pituitary gland parenchyma of salivary gland - Enamel of teeth - Lens - Inner ear ( Neuroectoderm) - Posterior pituitary - Pineal body - Retina - Central nervous system Mesoderm ( Intermediate plate) - Urogenital system ( Lateral plate) - Connective tissue (mesenchyme) - Muscles of viscera - Serous memberanes of pleura - Pericardium and peritoneum - Blood and lymph cells - Cardiovascular and lymphatic systems - Spleen - Adrenal cortex ( Paraxial) - Muscles of trunk - Skeleton - Dermis of skin - Connective tissue (mesenchyme) Endoderm - Epithelial components of trachea - Bronchi and lungs - Epithelium of gastrointestinal tract - Liver - Pancreas - Urinary bladder and urachus - Epithelial components of pharynx - Thyroid - Tympanic cavity - Pharyngotympanic tube - Tonsils and parathyroids Congenital malformations: These are defined as gross structural defects present at birth. Teratology is the study of such defects and teratogens are the factors that cause such abnormalities. 2-3% of all live born infants show one or more significant congenital malformations. Congenital malformations are now believed to be caused not only due to hereditary factors but also due to environmental factors or combination of both. Teratogens associated with human malformations include infectious agents and chemical agents some examples that have a direct effect on head and neck deformities are: 1. Rubella can cause cateracts and deafness 2. Herpes simplex can cause microcephaly 3. Phenytoin can cause facial defects and mental retardation 4. Trimethadione can cause cleft palate 5. Amphetamines can cause cleft lip and palate 6. Warfarin can cause chondrodysplasia and micro cephaly 7. Isotretinoin mandibular hypoplasia and cleft palate 8. Alcohol can cause cleft palate Chromosomal and genetic factors causing malformations include: 1. Trisomy 21 (Down's syndrome) can cause mental retardation 2. Treacher Collins syndrome can cause malar and mandibular hypopalsia and ear loss 3. Di George syndrome (catch 22) can also cause cleft palate along with absence of the thymus and parathyroid glands. These are only some examples and many more are present, which you the reader should be familiar with.