Lec1 Introduction to medical Embryology-Gametogenesis.pdf

College of Medicine Dr. Firas Al-Masoody Second stage Medical Embryology Lecture 1 Introduction to Medical Embryology- Gametogenesis Learning objectives:  Define embryology  State the importance of studying embryology  Explor...

College of Medicine Dr. Firas Al-Masoody Second stage Medical Embryology Lecture 1 Introduction to Medical Embryology- Gametogenesis Learning objectives:  Define embryology  State the importance of studying embryology  Explore the process of mitosis and meiosis  Identify the different stages of Gametogenesis (Spermatogenesis and oogenesis)  Outline the stages of Spermiogenesis What is Embryology? The study of developmental events that occur during the prenatal stage (prenatal= before birth). It’s very usfule or important to help understand Why study embryology? the cases of variation in the human Human embryology does not always occur normally. About 3-4% of all live-born children will be diagnosed eventually with significant malformation (i.e. birth defect). Therefore, understanding why human embryology goes wrong and results in birth defect requires understanding of the molecular genetics, cellular, and tissue events underlying normal embryology. Knowing human embryology also helps in understanding of adult anatomy and provides a bridge between basic science (e.g., anatomy and physiology) and clinical science (e.g., obstetrics, pediatrics, and surgery). Finally, it allow the physician to accurately advise patients on many issues, such as reproduction , contraception , prenatal development , in vitro fertilization , stem cells , and cloning. Periods of human embryology: 1. Embryonic period : The first 8 weeks following fertilization, is characterized by a large number of rapid changes. 2. Fetal Period : The period of the fetus extend from the 9th week until birth and involve rapid growth of the fetus and maturation of its organ system. Phases of human embryology Gametogenesis: conversion of germ cells into male and female gametes (egg, and sperm, respectively). Fertilization: the joining of the gametes to form the zygote. Cleavage: a series of rapid cell divisions Gastrulation: the rearrangement of cells into three primary germ layers- ectoderm, mesoderm, and endoderm. The body axes also become identifiable: dorsal-ventral, cranial- caudal, and medial-lateral axes. 1  Formation of the tube-within-a-tube body plan: body folding, of the embryonic disc into a C-shaped embryonic body consisting of an outer ectodermal tube (the future skin) and an inner endodermal tube (the gut tube), with the mesoderm between the two tubes. Organogenesis: the formation of organ rudiments and organ Systems. THE CHROMOSOME THEORY OF INHERITANCE Traits of a new individual are determined by specific genes on chromosomes inherited from the father and the mother. Humans have approximately 23,000 genes on 46 chromosomes. Genes on the same chromosome tend to be inherited together and so are known as linked genes. In somatic cells, chromosomes appear as 23 homologous pairs to form the diploid number of 46. There are 22 pairs of matching chromosomes, the 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 inherited from the maternal gamete, the oocyte, and one from the paternal the union of the gametes at fertilization restores the diploid number of 46. Ploidy and C-value: Ploidy (N) refers to the number of copies of each chromosome present in nucleus of cells. Normal human somatic cell contain 46 chromosomes (diploid or 2N). Normal gametes contain 23 chromosomes (Haploid or 1N). Euploid: refers to any exact multiple of N (eg. Diploid, triploid). Aneuploid: refers to any chromosome number that is not euploid. It is usually applied when an extra chromosome is present (Trisomy), or when one is missing (Monosomy). C value refers to the number of copies of double stranded DNA in the nucleus. Diploid cells= 2C or 4C (only before cell division) Haploid cells=1C Mitosis Mitosis is the process whereby one cell divides, giving rise to two daughter cells that are genetically identical to the parent cell. Each daughter cell receives the complete set of 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, and they cannot be recognized with the light microscope. With the onset of mitosis the chromosomes begin to coil, contract, and condense; these events mark the beginning of prophase. Each chromosome now consists of two parallel subunits, chromatids, that are joined at a narrow 2 region common to both called the centromere. Throughout prophase the chromosomes continue to condense, shorten, and thicken, but only at prometaphase do the chromatids become distinguishable. During metaphase the chromosomes line up in the equatorial plane, and their doubled structure is clearly visible. Each is attached by microtubules extending from the centromere to the centriole, forming the mitotic spindle. Soon the centromere of each chromosome divides, marking the beginning of anaphase, followed by migration of chromatids to opposite poles of the spindle. Finally, during telophase, chromosomes uncoil and lengthen, the nuclear envelope reforms, and the cytoplasm divides. Each daughter cell receives half of all doubled chromosome material and thus maintains the same number of chromosomes as the mother cell. Meiosis Meiosis is the cell division that takes place only in the germ cells to generate male and female gametes, sperm and egg cells, respectively. Meiosis requires two cell divisions, meiosis I and meiosis II, to reduce the number of chromosomes to the haploid number of 23. Meiosis I: As in mitosis, male and female germ cells (spermatocytes and primary oocytes) at the beginning of meiosis I replicate their DNA so that each of the 46 chromosomes is duplicated into sister chromatids (prophase stage). In contrast to mitosis, during metaphase homologous chromosomes then align themselves in pairs, a process called synapsis. The pairing is exact and point for point except for the XY chromosomes. 3 The homologous chromosomes form a joint structure called chiasma (composed of two chromosomes, consisting of four chromatids, and two centromeres). Chiasma formation makes it possible for the two homologous chromosomes to exchange large segments of DNA by a process called crossover. Crossovers: Crossovers, critical events in meiosis I, are the interchange of chromatid segments between paired homologous chromosomes. Segments of chromatids break and are exchanged as homologous chromosomes separate. There are approximately 30 to 40 crossovers (one or two per chromosome) with each meiotic I division and are most frequent between genes that are far apart on a chromosome. Crossover increases the genetic variability of future gametes. Homologous chromosomes then pull apart during anaphase and separate into two daughter cells during telophase. The centromeres of the chromosomes do not replicate; therefore the two chromatids of each chromosome remain together after meiosis I. The first meiotic cell division produces two secondary spermatocytes in the male and a secondary oocyte and a first polar body in the female. Meiosis II: Shortly thereafter meiosis II separates sister chromatids. No DNA replication occurs during the second meiotic division. The 23 chromosomes (each consisting of two chromatids) condense during the second meiotic prophase and line up during the second meiotic metaphase. The chromosomal centromeres then replicate, and during anaphase, the two chromatids of each chromosome pull apart into two chromosomes (each consisting of a single chromatid), one of which is distributed to each of the daughter nuclei. The second meiotic division produces two spermatids in the male and a large definitive oocyte and second polar body in the female. As a result of meiotic divisions: Genetic variability is enhanced through crossover (which redistributes genetic material), and the random distribution of homologous chromosomes to the daughter cells. Each germ cell contains a haploid number of chromosomes, so that at fertilization the diploid number of 46 is restored. 4 Clinical correlate: Chromosome abnormality: either numerical or morphological alteration in one or more chromosome affecting autosomes or sex chromosomes. They result in spontaneous abortion or abnormal development: Around 40% of conceptions ends in spontaneous abortion and that 40-50% of these abortions are due to major chromosomal anomalies. The most common chromosomal anomalies in abortuses are 45, X (Turner syndrome), triploidy, and trisomy 16. In meiosis, the pair of homologous chromosomes normally separate during the meiosis I, so that each daughter cell receive one member of each pair. Sometimes, however, separation does not occur (nondisjunction) and both member of the pair go into one cell. As a result of nondisjunction of the chromosomes, one cell receives 24 chromosomes and the other 22 instead of the normal 23. When at fertilization, a gamete with 23 chromosomes combine with a gamete having either 24 or 22 chromosomes, the result is an individual with either 47 chromosomes (Trisomy) or 45 chromosomes (monosomy). 5 GAMETOGENESIS Definitions: A. Gametogenesis: conversion of germ cells into male and female gametes (the sperm and egg). B. Sexual reproduction- when female and male gametes (oocyte and spermatozoon, respectively) unite at fertilization. C. Somatic (body) cells- Diploid cells-46 Chromosomes and formed by mitosis. D. Gametes (sperm and oocytes) Haploid cells-23 chromosomes and formed by Meiosis. Occurs in the gonads (Testes and ovaries). Embryo development begins with fertilization, the process by which the male gamete (sperm) and female gamete (oocyte) unite to give rise to a zygote. Cells that give rise to the gametes are called primordial germ cells (PGCs) first identified within the wall of the yolk sac during the 4th weeks of gestation. From the wall of the yolk sac, PGCs actively migrate between the 4th and 6th weeks of gestation to the dorsal body wall of the embryo, where they populate the developing gonads (Testes and Ovaries), and differentiate into the gamete precursor cells called spermatogonia in the male and oogonia in the female. Like the normal somatic cells of the body, the spermatogonia and oogonia are diploid contain 46 chromosomes. When these cells eventually produce gametes by the process of gametogenesis (called spermatogenesis in the male and oogenesis in the female), they undergo meiosis , a sequence of two specialized cell divisions by which the number of chromosomes in the gametes is halved. The gametes thus contain 23 chromosomes (one of each pair); therefore, 6 they are haploid. Gametogenesis also includes cytodifferentiation, resulting in the production of mature spermatozoa in the male and definitive oocytes in the female. Spermatogenesis Spermatogenesis is the process by which spermatogonia differentiate into mature spermatozoa. It occurs in the seminiferous tubules of the testes and begins at the age of puberty. In the human male, each cycle of spermatogenesis takes about 74 days At birth: PGCs can be recognized in the sex cords of the testis as large, pale cells surrounded by supporting cells (Sertoli cells). Shortly before puberty: The sex cords acquire a lumen and become the seminiferous tubules. At about the same time, PGCs give rise to spermatogonial stem cells. At regular intervals, cells emerge from this stem cell population and enters spermatogenesis. Spermatogenesis can be divided into 3 phases: A. Spermatocytosis: Spermatogonia proliferate by mitotic division to replace themselves and to produce primary spermatocytes. B. Meiosis: 2 successive cell divisions Meiosis I produces two secondary spermatocytes and meiosis II produces spermatids. C. Spermiogenesis: a series of changes resulting in the transformation of spermatids into spermatozoa include (a) Formation of the acrosome, which covers half of the nuclear surface and contains enzymes to assist in penetration of the egg during fertilization; (b) Condensation of the nucleus; (c) Formation of neck, middle piece, and tail; (d) Shedding of most of the cytoplasm 7 Structure of spermatozoa (singular spermatozoon) 1. Head- contain the nucleus and capped by acrosome which contain hydrolytic enzymes essential for fertilization. 2. Middle piece- containing mitochondria which generate energy for swimming 3. Tail- containing microtubules. Clinical correlate: Errors in spermatogenesis or spermiogenesis are common. Examination of a sperm sample will reveal spermatozoa with abnormalities such as small or narrow heads, double heads, acrosomal defects, and double tails. Presence of a larger number of abnormal spermatozoa (called teratospermia) can be associated with infertility. 8 Oogenesis Oogenesis is the process by which oogonia differentiate into mature oocytes. It occurs in the ovary and begins at three months of fetal development. Maturation of Oocytes Begins before Birth (pre-natal) Once primordial germ cells have arrived in the gonad female (ovaries), they differentiate into oogonia. These cells undergo a number of mitotic divisions and, by the end of the third month, are arranged in clusters surrounded by a layer of flat epithelial cells. Whereas all of the oogonia in one cluster are probably derived from a single cell, the flat epithelial cells, known as follicular Cells, originate from surface epithelium covering the ovary. The majority of oogonia continue to divide by mitosis, but some of them give rise to primary oocytes that enter prophase of the first meiotic division and become arrested at this stage. During the next few months, oogonia increase rapidly in number, and by the fifth month of prenatal development, the total number of germ cells in the ovary reaches its maximum, estimated at 7 million. At this time, cell death begins, and many oogonia as well as primary oocytes become atretic. By the seventh month, the majority of oogonia have degenerated except for a few near the surface. All surviving primary oocytes have entered prophase of meiosis I, and most of them are individually surrounded by a layer of flat epithelial cells. A primary oocyte, together with its surrounding flat epithelial cells, is known as a primordial follicle. Maturation of Oocytes Continues at Puberty The total number of primary oocytes at birth is estimated to vary from 700,000 to 2 million. At this stage, all primary oocytes have started prophase of meiosis I, but instead of proceeding into metaphase, they remain in prophase (the diplotene stage) and do not finish their first meiotic division before puberty is reached. During childhood most oocytes become atretic; only approximately 400,000 are present by the beginning of puberty, and fewer than 500 will be ovulated Some oocytes that reach maturity late in life have been dormant in the diplotene stage of the first meiotic division for 40 years or more before ovulation. 9