Ana 11: Embryology Gametogenesis PDF

ANA 11: EMBRYOLOGY GAMETOGENESIS Dr. Ferraris | August 17, 2023 TABLE OF CONTENTS I. Chromosome Theory of III. Morphological Changes Inheritance During Maturation of the...

ANA 11: EMBRYOLOGY GAMETOGENESIS Dr. Ferraris | August 17, 2023 TABLE OF CONTENTS I. Chromosome Theory of III. Morphological Changes Inheritance During Maturation of the A. Mitosis Gametes B. Meiosis A. Oogenesis II. Chromosomal and Genetic B. Spermatogenesis Abnormalities A. Numerical Abnormalities B. Structural Abnormalities I. CHROMOSOME THEORY OF INHERITANCE Chromatid: two copies of the same chromosome attached together Centromere: the primary constriction where the sister Figure 3. Cell cycle chromatids are attached; holds chromatid pair together A. MITOSIS Kinetochore: protein structure that assembles on the centromere and attaches sister chromatids to mitotic spindle ➔ is a nuclear division plus cytokinesis, and produces two identical daughter cells ➔ occurs in all somatic cells – diploid (2n) cells Figure 1. Parts of a chromosome (Source: National Human Genome Research Institute, 2023; Science Photo Library, 2023) Karyotype: complete set of chromosomes in a species; it is a process of analyzing the number and shape of a chromosome. Figure 4. Phases of mitosis (Source: University of Lanceister) 1. Interphase (G2) ➔ DNA replicates ➔ Centrioles, if present, replicate ➔ Cell prepares for division 2. Prophase ➔ Nuclear membrane disintegrates, and nucleolus disappears ➔ Chromosomes condense ➔ Mitotic spindle begins to form and is complete at the end Figure 2. Karyotype of prophase (Source: National Human Genome Research Institute, 2023) ➔ Kinetochores begin to mature and attach to spindle ➔ Females: possess XX 3. Metaphase ➔ Males: possess XY ➔ Kinetochores attach chromosomes to the mitotic spindle and align them along the metaphase plate at the equator Cell cycle: an ordered set of events, culminating in cell growth of the cell. and division into two daughter cells. Non-dividing cells are not considered to be in the cell cycle. 4. Anaphase ➔ Kinetochore microtubules shorten, separating chromosomes to opposite poles ➔ Polar microtubules elongate, preparing cell for cytokinesis Trans # 1 Group 10: Togupen, Ton-ogan, Villalobos, and Villasis TC: Togupen TH: Villalobos 1 of 8  5. Telophase Special Events in Meiosis ➔ Chromosomes reach poles of cell Synapsis or pairing of homologous chromosomes lengthwise. ➔ Kinetochores disappear Pairing is exact and point to point (except for X and Y ➔ Polar microtubules continue to elongate, preparing cell for chromosomes). cytokinesis Crossovers or interchange of chromatid segments between ➔ Nuclear membrane re-forms paired homologous chromosomes. Chiasma formation: the X like structure where points of ➔ Nucleolus reappears interchange of homologous chromosomes are temporarily ➔ Chromosomes decondense united. 6. Cytokinesis Phases of Meiosis I ➔ Plant cells: cell plate forms, dividing daughter cells A. Prophase I ➔ Animal cells: cleavage furrow forms at equator of cell and a. Leptotene: duplicated chromosomes start to condense pinches inward until cell divides in two b. Zygotene: formation of synaptonemal complex; synapsis begins c. Pachytene: synapsis is complete; crossing over occurs d. Diplotene: disappearance of synaptonemal complex; chiasma is now visible e. Diakinesis: bivalent is now ready for metaphase I; fragmentation of the nuclear envelope Figure 7. Stages of prophase I (Source: Bioninja) B. Metaphase I Figure 5. Phases of mitosis Paired homologous chromosomes align on the metaphase plate B. MEIOSIS C. Anaphase I → cell division that takes place in germ cells only Homologous chromosomes separate → Requires two cell divisions D. Telophase I → Diploid germ cells give rise to haploid (n) gametes Formation of two (2) daughter cells Figure 8. Summary of meiosis I (Source: Biology Dictionary) Phases of Meiosis II A. Prophase II: Spindle fibers reform and attach to the centromere Figure 6. Summary of meiotic divisions I and II B. Metaphase II: Chromosomes align at the centromere (Source: Choi, n.d.) C. Anaphase II: Chromatids divide at the centromeres and move toward the opposite poles D. Telophase II: Four haploid cells are formed containing half the number of the original homologous pair Trans # 1 Group 10: Togupen, Ton-ogan, Villalobos, and Villasis TC: Togupen TH: Villalobos 2 of 8  → True polyploidy rarely occurs in humans, although it occurs in some tissues (especially the liver). Aneuploid → Is any chromosome number that is not euploid → It is an abnormal number of chromosomes such as having a single extra chromosome (47) or a missing chromosome (45) → Aneuploid (not good) karyotypes are given names with the suffix “-somy”, (rather than “-ploidy”, used for euploid karyotypes) such as Trisomy and Monosomy NOTE: Polyploidy refers to a numerical change in the whole set of chromosomes, while Aneuploidy refers to a numerical change in Figure 9. Summary of meiosis II part of the chromosome. (Source: Biology Dictionary) Three Types of Numerical Chromosomal Abnormalities Significance of Meiosis a. Meiotic Nondisjunction Provides constancy of the chromosome number from b. Mitotic Nondisjunction generation to generation by reducing the chromosome number c. Chromosomal translocation from diploid to haploid, thereby producing haploid gametes. Allows random assortment of maternal and paternal 1. Meiotic Nondisjunction chromosomes between gametes. → May involve autosomes or sex chromosomes Relocates segments of maternal and paternal chromosomes → In females, incidence increases with age 35 years or by crossing over of chromosome segments, which “shuffles” more. the genes and produces a recombination of genetic material. Meiosis I: Two members of homologous chromosomes II. CHROMOSOMAL AND GENETIC ABNORMALITIES fail to separate and both members of a pair move into one cell. Causes of Birth Defects and Spontaneous Abortions Meiosis II: When sister chromatids fail to separate. a. Chromosomal abnormalities b. Genetic factors Incidence for Major Chromosomal Abnormalities → 50% of conceptions end in spontaneous abortions and 50% of these abortions have major chromosomal abnormalities → Thus approx. 25% of conceptuses have major chromosomal defects → Chromosomal abnormalities account for 7% of major birth defects; most common is Turner’s Syndrome → Gene mutations account for an additional 8% of cases → There are two types of chromosomal abnormalities that can occur during meiotic or mitotic divisions: Numerical and Structural A. NUMERICAL ABNORMALITIES Karyotype: refers to a full set of chromosomes from an individual which can be compared to a “normal” karyotype for the species via genetic testing. Figure 11. Meiotic nondisjunction Ploidy: the number of sets of chromosomes in a biological cell. Haploid = n (in normal gametes) 2. Mitotic Nondisjunction Diploid = 2n (in normal somatic cell) Mosaicism Euploid = An exact or multiple of n or of the monoploid number. → Some cells have abnormal chromosomal numbers and → A human with an abnormal but integral multiple of the others have normal monoploid number, (69 chromosomes) would also be → Occurs in the earliest cell divisions considered as euploid) → Affected individuals exhibit characteristics of particular → e.g. (2n, 3n, 4n, etc.) syndrome (e.g. Down syndrome in 1% of cases) → 3. Chromosomal Translocation → When a portion of one chromosome is transferred to another non homologous chromosome and a fusion gene is created. → There are two main types of translocations: Balanced and unbalanced. a. Balanced - An even exchange of material with no genetic information is extra or missing, and individual is normal. Figure 10. Types of ploidy - If no genetic material is lost during the exchange, Polyploid the translocation is considered to be a balanced → Many organisms have more than two sets of homologous translocation. chromosomes and are called polyploid. → A chromosome number that is a multiple of haploid number of 23 other than the diploid number (e.g., 69) Trans # 1 Group 10: Togupen, Ton-ogan, Villalobos, and Villasis TC: Togupen TH: Villalobos 3 of 8  Figure 14. Signs of Down Syndrome Figure 12. Balanced translocation 2. Trisomy 18 (Edward’s Syndrome) b. Unbalanced 1:5000; Infants usually die by age of 2 months - Where the exchange of genetic material is S/S: Mental retardation, congenital heart defects, low-set ears, unequal and part of one chromosome is lost & flexion of fingers altered phenotype is produced (Down syndrome in 4% of cases) Figure 15. Child with Trisomy 18 3. Trisomy 13 (Patau Syndrome) Figure 13. Unbalanced translocation 1:5000; most of the infants die by age 3 months → An entire chromosome has attached to another at the S/S: mental retardation, holoprosencephaly, congenital heart centromere. defects → Long q arms of two chromosomes (14 & 21) become joined at a single centromere. → 4% of cases of Down syndrome, unbalanced translocation can occur during meiosis I or meiosis II. Commonly Known Chromosomal Abnormalities 1. Down Syndrome (Trisomy 21) Causes: → Meiotic nondisjunction 95% (trisomy 21) → Unbalanced translocation 4% b/w 21 and 13, 14, 15 → Mosaicism due to mitotic nondisjunction 1% Incidence: → Female under 25 = 1:2000 → At 35 = 1: 300 Figure 16. Child with Trisomy 13 and its karyotype → At 40 = 1:40 Trans # 1 Group 10: Togupen, Ton-ogan, Villalobos, and Villasis TC: Togupen TH: Villalobos 4 of 8  4. Klinefelter’s Syndrome Chromosomal Deletion Have 47 chromosomes (XXY) & a sex chromatin Barr body or 48 A part of a chromosome is missing or “deleted”. (XXXY); more the number of X more the chances of mental Breaks are caused by environmental factors. impairment A very small piece of a chromosome can contain many different Cause: Nondisjunction of XX homolouge genes. Found only in males, detected at puberty When genes are missing, “instructions” are missing resulting in Incidence: 1 in 500 males errors in the development of a fetus. S/S: Sterility, testicular atrophy, hyalinization of seminiferous typically involve large deletions (Cri-Du-Chat syndrome) and tubules, gynecomastia. microdeletions (Angelman’s and Prader-Willi syndromes) 1. Cri-du-chat Syndrome Partial deletion of chromosome 5 S/S: High pitched cat-like cry, a small head size, low birth weight, mental retardation, and congenital heart disease. Figure 19. Child with Cri-du-chat Syndrome 2. Angelman’s Syndrome Figure 17. Signs of Klinefelter’s Syndrome caused by a microdeletion on the long arm of chromosome 15 (15q11-15q13). 5. Turner’s Syndrome Inherited on maternal chromosome 45 X karyotype S/S: Mental retardation, cannot speak, poor motor development, Only monosomy compatible with life epileptic seizures, and prolonged periods of laughter Causes: → Nondisjunction in male gamete 3. Prader-Willi Syndrome → Structural abnormalities of X chromosome Microdeletion on the long arm of chromosome 15 → One X chromosome is missing Inherited on paternal chromosome → Mitotic nondisjunction S/S: Obesity, mental retardation, hypogonadism, undescended testes, and cryptorchidism Figure 18. Signs of Turner’s Syndrome Figure 20. [A] Angelman’s syndrome; [B] Prader-Willi syndrome B. STRUCTURAL ABNORMALITIES Genomic Imprinting Occur when the chromosome’s structure is altered, this can take an epigenetic mechanism wherein the characteristics that are several forms: translocation, deletion, or duplication of differentially expressed depends upon whether the genetic chromosomes. material is inherited from the mother or the father. Chromosomes breaks occur either as a result of damage to DNA (by radiation or chemicals) or as part of the mechanism of → Angelman’s syndrome and Prader-Willi syndrome are recombination. examples of genomic imprinting. However, the total number of chromosomes is usually normal. Fragile X Syndrome Cause: → Genetic disorder caused by a break or weakness on the long arm of X chromosome. Trans # 1 Group 10: Togupen, Ton-ogan, Villalobos, and Villasis TC: Togupen TH: Villalobos 5 of 8  Incidence: → Dominant mutation → 1:5000, individuals with males affected more than females If a mutant gene produces an abnormality in a single (X-linked condition). dose, despite the presence of a normal allele. → 2nd most common inherited cause of mental retardation → Recessive mutation due to chromosomal abnormalities. If both genes are abnormal or if the mutation is X-linked S/S: Mental retardation, large ears, prominent jaw, and pale blue irises. Variations in the effects of mutant genes may be a result of modifying factors. In addition to causing congenital malformations, mutations can result in inborn errors of metabolism. These diseases, among which are: Phenylketonuria (PKU) Caused by a deficiency in the enzyme phenylalanine hydroxylase ▪ Loss of this enzyme result in mental retardation, organ damage, unusual posture and in some cases maternal PKU, severely compromise pregnancy Homocystinuria A methionine metabolism disease, can lead to abnormal accumulation of homocysteine and its metabolites in blood and urine Galactosemia Best known errors of metabolism and refer as the galactose in blood. Figure 21. [A] A typical physical characteristics of an individual with Group of inherited disorders that impairs body ability to process and FXS, including long, narrow face, a large head with large ears, and a produce energy from a sugar called galactose prominent forehead; [B] Karyotype of FXS from a normal chromosome. III. MORPHOLOGICAL CHANGES DURING MATURATION OF Other Continuous Gene Syndrome THE GAMETES can be inherited from either parent Examples: A. OOGENESIS → Miller-Dielter syndrome → Process whereby oogonia differentiate into mature oocytes, → S/S: lissencephaly, developmental delay, seizures, and The maturation of oocytes starts before birth and continues at puberty cardiac and facial abnormalities resulting from a deletion at 17p13 Figure 22. Facial photograph of a patient with Miller-Dieker syndrome. Typical facial features include prominent forehead, bitemporal Figure 23. Phases of Oogenesis hollowing, short nose with upturned nares, prominent upper lip and micrognathia (Wakiguchi et al., 2015) Maturation of Oocytes Before Birth After the arrival of the Primary Germ Cell (PGCs) in the ovary, → 22p11 syndrome (DiGeorge Syndrome) they will begin to differentiate into oogonia. Oogonia proliferates due to mitosis. a disorder caused when a small part of chromosome 22p11 By the 3rd month of development, they will arrange in clusters is missing. This deletion results in the poor development of and give rise to primary oocytes. several body systems ➔ The total number of primary oocytes at birth is S/S: palatal defects, conotruncal heart defects, speech estimated to vary from 600,000 to 800,000. delay, learning disorders, and schizophrenia-like disorder. As oocytes form, epithelial cells surround them and form a single flattened cell layer called the follicular cell. C. GENE MUTATIONS The majority of oogonia continue to divide by mitosis, but some Many congenital malformations in humans are inherited, and arrest their cell division in prophase I and form primary oocytes. some show a clear Mendelian pattern of inheritance. During the next few months, oogonia increased rapidly in Genes exist as pairs, or alleles, so there are two doses for each number. genetic determinant: one from mother and one from the father By the 5th month, the number of germ cells reached seven million and cell death (atresia) began. By the 7th month, the majority of oogonia have degenerated. Trans # 1 Group 10: Togupen, Ton-ogan, Villalobos, and Villasis TC: Togupen TH: Villalobos 6 of 8  All surviving primary oocytes have entered prophase I of meiosis I wherein most of them are individually surrounded by flat follicular epithelial cells. A primary oocyte, together with its surrounding flat epithelial cell, is called a Primordial follicle. Maturation of Oocytes Continues at Puberty All primary oocytes that enter prophase of Meiosis I will enter the Diplotene Stage where they are arrested until puberty. → Diplotene stage is a resting stage during prophase I, characterized by a lacy network of chromatin. → The arrested state is produced by oocyte maturation inhibitor (OMI), a small peptide secreted by follicular cells. Figure 24. [A] Primordial follicle consisting of a primary oocyte By puberty, only about 40,000 primary oocytes are present. surrounded by a layer of flattened epithelial cells; [B] Early primary or Fewer than 500 will be ovulated. preantral stage follicle recruited from the pool of primordial follicles. As the follicle grows, follicular cells become cuboidal and begin to secrete I. Pre-Antral Stage the zona pellucida; [C] Mature primary (preantral) follicle with follicular → During puberty, as primordial follicles grow, the follicular cells forming a stratified layer of granulosa cells around the oocyte and epithelial cells change from flat to cuboidal in shape and the presence of a well-defined zona pellucida. (Source: Sadler, 2015) proliferate to produce a stratified epithelium of granulosa cells forming the Primary Follicle. → Granulosa Cells: Separate the surrounding connective tissue of the ovary which forms Theca Follica. Together with the oocyte, they secrete a layer of glycoproteins on the surface, forming the Zona Pellucida → As follicles grow, Theca Folliculi organize into 2 layers, the theca interna and theca externa II. Antral/Vesicular follicle → Each month, 15 to 20 follicles selected from a pool of growing follicles begin to mature. → Some of the follicles die, whereas others begin to accumulate fluid in a space called the antrum entering the antral or vesicular stage. The follicle is termed a vesicular Figure 25. [A] Vesicular and [B]Mature vesicular (graafian) follicles or an antral follicle. (Source: Sadler, 2015) III. Mature Vesicular (Graafian) follicle → Can grow 25 mm or more in size B. SPERMATOGENESIS → It is surrounded by the theca interna and theca externa Maturation of sperm begins at puberty. ▪ Theca interna: inner layer of secretory cells, and The process involves all of the events by which spermatogonia composed of cells having characteristics of steroid are transformed into spermatozoa. secretion ▪ Theca externa: outer fibrous capsule, and gradually merges with the ovarian connective tissue → Fluid continúes to accumulate such that, immediately prior to ovulation, follicles are quite swollen and are called mature vesicular follicles or graafían follicles. → Granulosa cells surrounding the oocyte remains intact and form the cumulus oophorus → With each ovarian cycle, a number of follicles begin to develop, but usually, only one reaches full maturity → Surge in the luteinizing hormone (LH) induces the preovulatory growth phase and completes Meiosis I. ▪ This results in formation of two daughter cells, each with 23 double-structured chromosomes → The secondary oocyte receives most of the cytoplasm whereas the first polar body receives none. ▪ The first polar body lies between the zona pellucida and the cell membrane of the secondary oocyte in the perivitelline space. → The cell will proceed to Meiosis II but will only be completed Figure 26. Phases of Spermatogenesis if the oocyte is fertilized. → AT BIRTH: germ cells in the male infant can be recognized in the sex cords of the testis as large, pale cells surrounded by supporting cell. Supporting cells are derived from the surface epithelium of the testis in the same manner as follicular cells, become sustentacular cells, or Sertoli cells. → BEFORE puberty: the sex cords acquire a lumen and become the seminiferous tubules. → PGCs give rise to spermatogonial stem cells. → INITIATION: production of type A spermatogonia from the cells emerging from the stem cell population. Trans # 1 Group 10: Togupen, Ton-ogan, Villalobos, and Villasis TC: Togupen TH: Villalobos 7 of 8  Type A cells undergo a limited number of mitotic b. condensation of the nucleus; divisions to form clones of cells. c. formation of neck, middle piece, and tail; and → LAST CELL DIVISION: production of type B spermatogonia, d. shedding of most of the cytoplasm as residual bodies which then divide to form primary spermatocytes that are phagocytized by Sertoli cells. → Primary spermatocytes then enter a prolonged prophase (22 → When fully formed, spermatozoa enter the lumen of days) followed by rapid completion of meiosis I and formation seminiferous tubules. of secondary spermatocytes → From there, they are pushed toward the epididymis by → During the SECOND MEIOTIC DIVISION, these cells contractile elements in the wall of the seminiferous tubules. immediately begin to form haploid spermatids → Although initially only slightly motile, spermatozoa obtain full motility in the epididymis. In humans, the time required for a spermatogonium to develop into a mature spermatozoon is approximately 74 days, and approximately 300 million sperm cells are produced daily Figure 13. Transformation of spermatid to spermatozoa (Source: Sadler, 2015) REFERENCES Choi, E. (n.d.). Chapter 15 Blog: The Eukaryotic Cell Cycle, Mitosis, And Meiosis. In Health Science Academy. http://academygenbioii.pbworks.com/w/page/36196386/Chapter%20 15%20Blog%3A%20The%20Eukaryotic%20Cell%20Cycle%2C%20 Mitosis%2C%20And%20Meiosis%20%28Erica%29 Dutra, A. (2023). Karyotype. In National Human Genome Research Institute. https://www.genome.gov/genetics-glossary/Karyotype Meiosis. (2020). In Biology Dictionary. https://biologydictionary.net/meiosis/ Morris, S. (2023). Chromatid. In National Human Genome Research Institute. https://www.genome.gov/genetics-glossary/Chromatid Phases of Mitosis. (n.d.). In University of Lanceister. http://www2.le.ac.uk/departments/genetics/vgec/schoolscolleges/topi cs/cellcycle-mitosis-meiosis Figure 27. Type A spermatogonia, derived from the spermatogonial Sadler, T. W. (2015). Langman’s Medical Embryology 13th Edition. stem cell population, represent the first cells in the process of Shockey, G. (2023). Chromosome Structure, Illustration. In Science spermatogenesis until they become spermatozoa. Clones of cells are Photo Library. established, and cytoplasmic bridges join cells in each succeeding https://www.sciencephoto.com/media/1137003/view/chromosome- division until individual sperm are separated from residual bodies. structure-illustration (Source: Sadler, 2015) Stages of Prophase. (n.d.). In Bioninja. https://ib.bioninja.com.au/higher-level/topic-10-genetics-and- Spermatogenesis is regulated by Luteinizing Hormone (LH) evolu/101-meiosis/stages-of-prophase.html production by the pituitary gland. LH binds to receptors on Fragile X syndrome (Fraxa & FRAXE). Intergenetics. (2020, January Leydig cells and stimulates testosterone production, which in 17). https://intergenetics.eu/en/exam/fragile-x-syndrome-fraxa-fraxe/ turn binds to Sertoli cells to promote spermatogenesis. Encyclopedia Britannica, inc. (n.d.). Fragile-X syndrome. Follicle-stimulating hormone (FSH) is also essential Encyclopædia Britannica. because its binding to Sertoli cells stimulates testicular fluid https://kids.britannica.com/students/article/fragile-X- production and synthesis of intracellular androgen receptor syndrome/323777 proteins. Wakiguchi, C., Godai, K., Mukaihara, K., Ohnou, T., Kuniyoshi, T., Masuda, M., & Kanmura, Y. (2015). Management of general SPERMATOGENESIS anesthesia in a child with Miller–Dieker Syndrome: A case report. JA → Includes all the events by which spermatogonia are Clinical Reports, 1(1). https://doi.org/10.1186/s40981-015-0017-2 transformed into spermatozoa a. formation of the acrosome covers half of the nuclear surface and contains enzymes to assist in penetration of the egg and its surrounding layers during fertilization Trans # 1 Group 10: Togupen, Ton-ogan, Villalobos, and Villasis TC: Togupen TH: Villalobos 8 of 8