General Embryology PDF

Course Outline Primordial germ cell- origin and migration of the sex cells, colonisation of the presumptive gonads, growth and differentiation Development and organization of the testis and ovary Oogenesis and ovulation, meiotic changes in oocytes, formation and functions of the zona pellu...

Course Outline Primordial germ cell- origin and migration of the sex cells, colonisation of the presumptive gonads, growth and differentiation Development and organization of the testis and ovary Oogenesis and ovulation, meiotic changes in oocytes, formation and functions of the zona pellucida, follicular growth, pre- ovulatory, post ovulatory atresia, ovum maturation Spermatogenesis. Testis before and at puberty, seminiferous epithelium. Spermatozoa, spermatogenic cycle and time rotations in spermatogenesis Cycles and seasons – puberty, oestrous and menstrual cycles, ovulation Fertilization, egg and sperm transport, sperm penetration Pre-embryonic period, trophoblast and inner cell mass. Cell differentiation, fetal membranes Implantation and formation of placenta, placenta at birth, nutrition and protection of embryo Embryogenesis, differentiation of the embryonic area, formation of primary axial structures, differentiation of the intra-embryonic mesoderm, germ layers and their derivatives 1 EMBRYOLOGY (Developmental anatomy) Study of prenatal development of embryos and fetuses. Structural changes of a person from fertilization to adulthood; it includes embryology, fetology, and postnatal development. Teratology Division of embryology and pathology that deals with abnormal development (birth defects). Concerned with genetic and environmental factors that disturb normal development 2 Embryology is related to: Cellular and molecular description of human development in utero (life before birth Developing structures and functions Development of human gametes (spermatozoa and oocytes) Stem cells and progeny of cells and tissues Birth defects ART (Assisted Reproduction Technologies) 3 4 5 6 7 8  Conceptus: product of conception at any point between fertilization and birth Abortus: Immature placental or fetal tissue prematurely passed or curetted Ontogeny: total life period of an organism Genetics: to evaluate the role of heredity and environment in shaping up the new born Oocyte (ovum): a mature secondary female sex cell ready for fertilization Zygote: diploid, fertilized cell which has the potential to produce an embryo Cleavage: continous, rapid mitotic cell divisions occurring in zygote just after fertilization 9  Morula: as a sresult of cleavage, zygote appears like a mulberry bush consisting of small tightly packed cells. Embryo: first eight weeks of developing human when the primordia of almost all the organs and system have appeared Fetus: ninth week till birth which is marked by differentiation, growth of tissues and organs and weight gain. Primordium: first sign of the development of a new organ/region. With more differentiation and growth, the structure changes to primary, secondary or definitive etc CR Length and CH Length: measurement from vertex (cranium) to the rump or from the crown to the heels (CH Length). 10  Importance of Embryology Bridges the gap between prenatal development and other aspects of medicine Develops knowledge concerning the beginnings of life and the changes occurring during prenatal development Helps to understand the causes of variations in human structure Illuminates gross anatomy and explains how normal and abnormal relations develop Supports the research and application of stem cells for treatment of certain chronic diseases 11 Primordial Germ Cells (PGCs) Development begins with fertilization Gametes are derived from primordial germ cells formed in the epiblast during the second week and move to the wall of the yolk sac. Germ cells migrate in the fourth week from the yolk sac to reach the gonad by the end of the fifth week. Proliferate by mitosis reaching to 2000-5000 cells, during and after their migration PGCs interact with a range of cell types as they 12 Specification Cell fate determination – how a particular cell develops into a final cell type Migration Process of distribution of PGCs throughout the embryo during development PGCs are among the first lineages that are established in development and they are the precursors for gametes Migration starts in the posterior end of the embryo Movement is initially passive, movement becomes active as PGCs move towards the developing gonads PGCs could contain defects that could have a negative impact on later development – genetic mutations 13 Primordial Germ Cell Migration 14  Negative selection process – PGCs that are unable to complete migration are removed and those that are able to correctly respond to migration cues are preferred PGCs that migrate fastest reach the gonads and colonize it and give rise to future gametes PGCs that go off route or don’t reach the gonads undergo programmed cell death (apoptosis) Proliferation Leads to an increase in cell number and is a rapid mechanism of tissue growth Occurs in the gonads Functions of PGC migration Allow the cells to reach the gonads, where they will go on to form sperm or oocytes Serve as quality control for PGCs 15 16 CLINICALLY ORIENTED PROBLEMS What is the human embryo called at the beginning of its development? How do the terms conceptus and abortus differ? What sequence of events occurs during puberty? Are they the same in males and females? What are the respective ages of presumptive puberty in males and females? How do the terms embryology and teratology differ? 17  Differentiation - development of a fertilized egg cell to form a complex, multicellular organism involving cellular replication, growth and specialization for a variety of functions. Fertilized egg divides by mitosis to produce two genetically identical daughter cells, each of which divides to produce two more daughter cells and so on. These daughter cells specialize and produce the terminally differentiated cells of mature tissues, such as muscle or skin cells. 18  Most tissues retain undifferentiated cells (stem cells) that are able to divide and replace the differentiated cell population as required. Interval between mitotic divisions is known as the cell cycle. All body cells divide by mitosis except for male and female germ cells, which divide by meiosis to produce gametes 19 Cell division Chromosomes are distributed to the daughter cells. Phase between two mitoses is interphase. Chromosomes are duplicated in S phase Dividing cell is cleaved into genetically identical daughter cells by cytoplasmic division or cytokinesis. 20 Interphase Duplication of the centrosomes and centrioles starts in the interphase, before mitosis. Centrosome divides during interphase Divided into four phases: G0, G1 (presynthesis), S (DNA synthesis), and G2 (post-DNA duplication). S phase - Synthesis of DNA - Duplications of the centrosomes with their centrioles. 21 Cell Cycle Alternation between mitosis and interphase known as the cell cycle occurs in all tissues with cell turnover. DNA replication occurs during interphase Cell cycle can be divided into two stages: mitosis, consisting of the four phases: (prophase, metaphase, anaphase, and telophase), and interphase (Go, S, G1, G2). 22 23 Interphase Resting phase of the cell cycle Time during which the cell prepares for division by undergoing both cell growth and DNA replication. Occupies around 95% time of the overall cycle. Divided into three phases 24 G1 phase (presynthesis) (Gap 1) Phase of the cell between mitosis and initiation of replication of the genetic material of the cell. Cell is metabolically active and continues to grow without replicating its DNA. Varies in duration in bone tissue it lasts 25 h. Cell either continues the cycle or enters a quiescent phase called G0. Checking or restriction point (R) in G1 stops the cycle under unfavorable conditions. After the restriction point, the cycle continues through the synthetic phase (S) and the G2 phase. Intense synthesis of RNA and proteins, In cells that are not continuously dividing, the activities of the cell cycle may be temporarily or permanently suspended. 25 Go Phase Cell either continues the cycle or enters a quiescent phase called G0. Cells in such a state (eg, muscle, nerve) are referred to as being in the G0 phase. 26 S phase (Synthesis) DNA replication takes place during this phase. Centriole also divides into two centriole pairs in the cells which contain centriole. DNA synthesis lasts about 8 h. 27 G2 phase Accumulation of energy to be use during mitosis Synthesis of tubulin to be assembled in mitotic microtubules During this phase, the RNA, proteins, other macromolecules required for multiplication of cell organelles, spindle formation, and cell growth are produced as the cell prepares to go into the mitotic phase. Checkpoint at which the cell remains until all DNA synthesized with defects is corrected. Lasts 2.5-3 h. Accumulation of the protein complex maturation promoting factor (MPF) that induces the beginning of mitosis, the condensation of the chromosomes, the rupture of the nuclear envelope, and other events related to mitosis. 28 M phase Complete reorganization to give birth to a progeny that has the same number of chromosomes as the parent cell. Other organelles are also divided equally by the process of cytokinesis which is preceded by mitotic nuclear division. The mitotic phase is divided into four overlapping stages:- Prophase, Metaphase, Anaphase, and Telophase Cytokinesis In this phase, the cytoplasm of the cell divides. It begins as soon as the mitosis ends. 29 Mitosis Process by which an eukaryotic cell separates the nuclear DNA and chromosomes and divides into two different but similar sets that are genetically identical to the parent. Chromosomes are pulled apart by a mitotic spindle, which is a specialized structure consisting of microtubules. Each daughter cell receives 46 chromosomes. Before a cell enters mitosis, each chromosome replicates its deoxyribonucleic acid (DNA). During this replication phase the chromosomes are extremely long, they are spread diffusely through the nucleus. 30 Prophase Chromosomes become visible within the nucleus. Gradual coiling of chromatin Chromosomes are condensed and shortened Chromatids are joined together at the centromere Centrosomes with their centrioles separate and migrate to each pole of the cell. Microtubules of the mitotic spindle appear between the two centrosomes Nuclear envelope and nucelolus disintegrates Centromere divides and centrioles move to the opposite poles of the cell. Centrioles form microtuules of the mitotic spindle Microtubules attach to kinetochores of chromatids and align chromosomes in the middle of the cell Cell division requires the mitotic apparatus. At the end of prophase, the nuclear envelope is broken by phosphorylation of the nuclear lamina proteins. 31 Metaphase Nuclear envelope disintegrates Chromosomes migrate to the equatorial plane of the cell Chromosome divides to form two sister chromatids. Chromatids attach to the microtubules of the mitotic spindle at the kinetochore Kinetochore - Controls entry of the cell into anaphase so that the process of mitosis does not progress until all chromatid pairs are aligned at the cell equator - metaphase checkpoint - Prevents daughter cells with unequal numbers of chromosomes. Chromosomes are arranged in the equatorial or metaphase plate. 32 Anaphase Sister chromatids split at the centromere from each other Migrate toward the opposite poles of the cell, pulled by microtubules. Centromeres move away from the center, pulling the remainder of the chromosome along. Mitotic spindle lengthens by addition of tubulin subunits to its interpolar microtubules while astral microtubules joining the centrosome to the cell cortex shorten. Centrioles are pulled apart and the chromatids are drawn to opposite ends of the spindle. By the end of anaphase, two groups of identical chromosomes are clustered at opposite poles of the cell. 33 Telophase Reappearance of nuclei in the daughter cells Chromosomes revert to their semidispersed state Nuclear envelope reassembles and nucleoli become apparent. Chromosomes uncoil. Plane of cytoplasmic division is the spindle equator Plasma membrane around the spindle equator becomes indented to form the cleavage furrow Cytokinesis occurs as a result of contraction of microfilaments present beneath the surface of the cleavage furrow. In early G1 phase, the mitotic spindle disaggregates and centrioles duplicate in preparation for the next mitotic division. 34 35 36 Chromosomes during mitosis Nuclei of all somatic cells of an individual contain deoxyribonucleic acid (DNA), called the genome. DNA is arranged into chromosomes consisting of deoxyribonucleotides with a double-stranded (helical) structure. Each strand consists of alternating deoxyribose S and phosphate P moieties. Each deoxyribose unit is covalently bound to a purine or pyrimidine base Bases are of four types, adenine A, cytosine C, thymine T and guanine G 37 38  46 chromosomes (the diploid number) comprising 22 homologous pairs, the autosomes, and 2 sex chromosomes, either XX in the female or XY in the male. During S phase, each chromosome is duplicated. Identical chromosomes known as chromatids are attached to one another at the centromere DNA molecule in each chromosome binds to histone proteins and hold the chromosome within the nucleus. Karyotyping - examination of the chromosomes of dividing cells - Gives diagnostic information about the chromosomal complement of an individual or of a malignant tumour 39 Karyotype 40  Stem cells - dividing cells / undifferentiated cells in tissues with a regular turnover of cells, Totipotent - embryonic stem cells that able to differentiate into any other cell type Multipotent - stem cells found in adults that are able to produce cells of several lineages eg haemopoeitic stem cell Unipotent - producing only a single cell type eg epidermal stem cells of the skin that produce only epithelial cells. Pluripotent – ability to form all three of the basic body layers and germ cells Cells are used in the treatment of degenerative diseases. - Ethics - use of embryonic cells. 41 MEIOSIS Cell division that takes place in the germ cells to generate male and female gametes Requires two cell divisions, meiosis I and meiosis II, to reduce the number of chromosomes to the haploid number of 23. As in mitosis, at the beginning of meiosis I replicate their DNA. In contrast to mitosis, homologous chromosomes align in pairs, a process called synapsis. Homologous pairs separate into two daughter cells. Meiosis II separates sister chromatids. 42 Crossover Critical events in meiosis I Interchange of chromatid segments between paired homologous chromosomes. Segments of chromatids break and are exchanged as homologous chromosomes separate. Points of interchange are temporarily united and form an X-like structure, a chiasma. As a result of meiotic divisions: (a) genetic variability is enhanced through crossover, which redistributes genetic material (b) each germ cell contains a haploid number43 First and second meiotic 44 Polar Bodies During meiosis one primary oocyte gives rise to four daughter cells, each with 22 plus 1 X chromosomes. Only one of these develops into a mature gamete, the oocyte; the other three, the polar bodies, receive little cytoplasm and degenerate Similarly, one primary spermatocyte gives rise to four daughter cells, two with 22 plus 1 X chromosomes and two with 22 plus 1 Y chromosomes. In contrast to oocyte formation, all four 45 46  Clinical Correlates Birth Defects and Spontaneous Abortions Chromosomal abnormalities, which may be numerical or structural. The most common chromosomal abnormalities in abortuses are 45,X (Turner syndrome), triploidy, and trisomy 16. Chromosomal abnormalities account for 7% of major birth defects, and gene mutations account for an additional 8%. 47 Chromosome Theory of Inheritance Humans have approximately 35,000 genes or 46 chromosomes. In somatic cells, chromosomes appear as 23 homologous pairs to form the diploid number of 46. 22 pairs of chromosomes (autosomes) and one pair of sex chromosomes. If the sex pair is XX, the individual is genetically female; if the pair is XY, the individual is genetically male. One chromosome of each pair is derived from the maternal gamete and one from the paternal gamete. Each gamete contains a haploid number of 23 48 Numerical Abnormalities Normal human somatic cell contains 46 chromosomes; the normal gamete contains 23. Normal somatic cells are diploid, or 2n; normal gametes are haploid, or n. Euploid refers to any exact multiple of n, e.g., diploid or triploid. Aneuploid refers to any chromosome number that is not euploid; usually when an extra chromosome is present (trisomy) or when one is missing (monosomy). Abnormalities may originate during 49  In meiosis, two members of a pair of homologous chromosomes should separate during the first meiotic division, sometimes, separation does not occur (nondisjunction), and both members of a pair move into one cell. As a result one cell receives 24 chromosomes, and the other receives 22 instead of the normal 23. When, at fertilization, a gamete having 23 chromosomes fuses with a gamete having 24 or 22 chromosomes, the result is an individual with either 47 chromosomes (trisomy) or 45 chromosomes (monosomy). Nondisjunction occurs mostly in meiosis and may involve the autosomes or sex chromosomes. Occasionally nondisjunction occurs during mitosis in an embryonic cell. Such conditions produce mosaicism, with some cells having an abnormal chromosome number and others being normal. 50 51 Translocation When chromosomes break, pieces of one chromosome attach to another. Such translocations may be balanced, in which case breakage and reunion occur between two chromosomes but no critical genetic material is lost and individuals are normal Or they may be unbalanced, in which case part of one chromosome is lost and an altered phenotype is produced. For example, unbalanced translocations in chromosomes 14 and 21 during meiosis produce gametes with an extra copy of 52 TRISOMY 21 (DOWN SYNDROME) Caused by an extra copy of chromosome 21 resulting from meiotic nondisjunction mostly during oocyte formation. Features include growth retardation; varying degrees of mental retardation; craniofacial abnormalities, facies, and small ears; cardiac defects; and hypotonia. The incidence is approximately 1 in 2000 conceptuses for women under age 25; 1 in 300 at age 35 and 1 in 100 at age 40. 53 Children with Down syndrome 54 TRISOMY 18 Features include mental retardation, congenital heart defects, low-set ears, and flexion of fingers and hands, micrognathia, renal anomalies, syndactyly, and malformations of the skeletal system. The incidence is approximately 1 in 5000 newborns. TRISOMY 13 Features include mental retardation, holoprosencephaly, congenital heart defects, deafness, cleft lip and palate,and eye defects, such as microphthalmia, anophthalmia, and coloboma. The incidence is approximately 1 in 20,000 55 56 KLINEFELTER SYNDROME Found only in males and usually detected at puberty, are sterility, testicular atrophy, hyalinization of the seminiferous tubules, and usually gynecomastia. Cells have 47 chromosomes with a sex chromosomal complement of the XXY or XXXY type, and a sex chromatin body (Barr body: formed by condensation of an inactivated sex chromosome The incidence is approximately 1 in 500 males. Nondisjunction of the XX homologues is the 57 TURNER SYNDROME A 45, X karyotype, is the only monosomy compatible with life. The few that survive are female and are characterized by the absence of ovaries (gonadal dysgenesis) and short stature, webbed neck, lymphedema of the extremities, skeletal deformities, and a broad chest with widely spaced nipples. In 80% of these women, nondisjunction in the male gamete is the cause. In the remainder of women, structural abnormalities of the X chromosome or mitotic nondisjunction resulting in mosaicism are the cause. TRIPLE X SYNDROME 58 Structural chromosome abnormalities Involves one or more chromosomes, usually resulting from chromosome breakage. Breaks are caused by environmental factors, such as viruses, radiation, and drugs. In some cases, the broken piece of a chromosome is lost, and the infant with partial deletion of a chromosome is abnormal. A well-known syndrome, caused by partial deletion of the short arm of chromosome 5, is the cri-du-chat syndrome. Such children have a catlike cry, microcephaly, mental retardation, and congenital heart disease. 59 Microdeletions May result in microdeletion syndrome or contiguous gene syndrome. An example of a microdeletion occurs on the long arm of chromosome 15. Inheriting the deletion on the maternal chromosome results in Angelman syndrome, and the children are mentally retarded, cannot speak, exhibit poor motor development, and are prone to unprovoked and prolonged periods of laughter If the defect is inherited on the paternal chromosome, Prader-Willi syndrome is produced; affected individuals are 60 61 62 Fragile sites Regions of chromosomes that demonstrate a propensity to separate or break under certain cell manipulations. Long arm of the X chromosome has been correlated with an altered phenotype and is called the fragile X syndrome. - Characterized by mental retardation, large ears, prominent jaw, and pale blue irides. - Males are affected more often than females - (1/1000 versus 1/2000), which may 63 Gene Mutations Birth defects attributable to a change in the structure or function of a single gene is called single gene mutation. Genes exist as pairs, or alleles, one from the mother and one from the father. If a mutant gene produces an abnormality in a single dose, it is a dominant mutation. If both alleles are abnormal (double dose) or if the mutation is X-linked in the male, it is a recessive mutation. 64 Diagnostic Techniques for Identifying Genetic Abnormalities Cytogenetic analysis High resolution metaphase banding techniques Fluorescence in situ hybridization (FISH) Spectral karyotype analysis 65