Topic 1-4

• • Aristotle proposed the modeling principle of any organism as "energia" or "entelecheia" with the ultimate energy called its psyche or soul
  • Aristotle proposed 3 types of soul operating in the organism: vegetative, animal, and spiritual
• History of Developmental Biology as a Science:

  • Started as an old science, one of the first
  • Dawn of biology in ancient Greece with Aristotle (384 - 322 BC) being the first to study embryos focused on chick
  • Aristotle proposed possible organs of an organism including spontaneous generation, hermaphroditism, and bisexual reproduction
  • Aristotle believed that the semen provides the "force" towards development and the menstrual blood provided the matter
  • Aristotle proposed the male as the "dynamic element" and the female as the "matter"
  • Aristotle's influence of religion is very strong
• Renaissance of Developmental Biology:

  • William Harvey (1578 - 1657) proposed that all organisms came from an egg
  • Harvey's proposal: Omne vivum ex ovum
  • Spermists claimed that the embryo comes from one sperm only, disputed by physics
  • Ovists claimed that all generations will come from one egg only, disputed by physics
  • Theory of preformation arose with ovists and spermists
  • Leeuwenhoek (1632 - 1723) and Hartsoeker claimed to have seen little men inside individual spermatozoa
  • Lazaro Spallanzani (1729 - 1799) observed that the female egg develops only in the presence of male semen
• • Oscar Hertwig (1875) proposed that both sperm and egg contribute to form an embryo
  • Epigenesist theory proposed by Caspar Friedrich Wolff (1738 - 1794)
  • Vitalism proposed that a vital force specific to life is the prime mover for the grand unfolding of the organism
• Comparative Embryology:

  • Karl Ernst von Baer (1792 - 1876) discovered eggs in many mammalian species and performed comparative studies
  • Ernst Haeckl (1834 - 1919) built on von Baer's study and proposed the controversial biogenetic law
  • Embryo Resemblances proposed by von Baer: all vertebrates pass through the same stages and possess similar structures that will later differentiate
• Era of Experimental Embryology:

  • E.B. Wilson recognized that embryonic development is a manifestation of changes in the cell
  • T.H. Morgan and Wilson debated on whether the determinants of development came from the nucleus or cytoplasm
  • August Weismann proposed the germ plasm theory
  • Wilhelm Roux was the Father of Experimental Developmental Biology and manipulated zygotes or oocytes
  • Hans Driesch perfected Roux's experiments
  • Theodore Boveri and Sutton proposed the chromosome theory
  • Gregor Mendel rediscovered paper on hereditary traits
• Studies of Genetics and Unresolved Issues:

  • Geneticists must provide evidence that genes control early stages of development of structures, not just terminal stages
  • Birth of Modern Genetics caused a deep divide leading to the establishment of genetics as a science
  • Unresolved issues include how genes determine hereditary traits, how the nucleus regulates metabolism, and how chromosomes direct different types of cytoplasm
  • Geneticists separated into those who believed in chromosomes as morphogenetic guides and those who believed in cytoplasm
• The Molecular Biology Revolution:

  • Middle of the 20th century provided means to study the role of genes in development
  • Powerful techniques like Knock out and knock in genes and PCR were developed
  • Drosophila sp. and Caenorhabditis elegans were key model systems in molecular biology
  • Understanding the principles in invertebrates can apply to more advanced organisms
• Spermatogenesis:

  • Histology of the Vertebrate Testes:
  • Frog testis has tunica albuginea, seminiferous tubules, and spermatocytes
  • Mouse testis has cyclical arrangement with spermatogonia, primary and secondary spermatocytes
  • Phases of Spermatogenesis include Spermatocytogenesis, meiosis, and Spermiogenesis
  • Metaphase and Anaphase differences in meiosis 1 and meiosis 2
• Phases of Spermiogenesis:
• Golgi phase:

  • Small PAS positive granules form within a vacuole (proacrosomal vesicle) in the Golgi complex
  • Centrioles migrate near the cell surface at the side opposite the future acrosome, initiating the formation of the flagellar axoneme
• Cap phase:

  • Acrosomal granule covers the nucleus, becoming the acrosomal cap
  • Acrosome contains hydrolytic enzymes to digest the corona radiata and the zona pellucida of the ovum
• Acrosomal phase:

  • Anterior pole becomes oriented towards the basement membrane of the seminiferous tubule
  • Nucleus becomes more elongated facilitated by the manchette
  • Mitochondria migrate towards the midpiece
• Kartagener syndrome:

  • Characterized by immobile flagella due to a mutation in dynein, a motor protein associated with microtubules
  • Mutation can lead to immotile sperm and cilia in the respiratory tract and fallopian tube
• Maturation phase:

  • Residual cytoplasm is removed
  • Golgi phase involves acrosomal vesicles melting the egg membrane and forming the egg of the sperm
  • Cap phase is relevant in cases of Kartagener syndrome
  • Acrosomal phase marks the orientation of the anterior pole towards the basement membrane
• The Spermatozoon:
• Different shapes exist according to species

  • The duration from spermatogonia to spermatozoa varies
  • Immature and mature spermatozoa are observed in different species
• The cycle and wave arrangement of spermatogenic cells:

  • Sperm can be continuously delivered as one discharges, another is ready to follow
  • Sperm delivery is not seasonal and remains fertile as long as healthy
  • Specific cellular associations are seen in humans with 6 stages
  • A group of sperm can be readily released at any stage
  • Each segment is undergoing a cycle
• Duration of spermatogenesis (days) in different species:

  • Mouse: 8.6 days for a cycle, 34.5 days for spermatogenesis
  • Hamster: 8.7 days for a cycle, 35 days for spermatogenesis
  • Sprague-Dawley rat: 12.9 days for a cycle, 51.6 days for spermatogenesis
  • Wistar rat: 13.3 days for a cycle, 53.2 days for spermatogenesis
  • Man: 16 days for a cycle, 70 to 74 days for spermatogenesis (4.5 cycles)
• Supporting Cells - The Sertoli Cells:
• Structure:

  • Sertoli cells do not divide during the reproductive period
  • They are resistant to infection, X-ray irradiation, and malnutrition
  • All growing spermatids are associated with Sertoli cells
  • Sertoli cells are involved in maintaining the blood-testis barrier
• Functions:

  • Support includes protection and nutritional regulation of developing spermatozoa
  • Phagocytosis of residual cytoplasm
  • Secretion of various substances including ABP under the influence of testosterone and FSH
  • Conversion of testosterone to estradiol
  • Production of Inhibin to suppress FSH release
  • MDIF promotes regression of Mullerian duct
• The Blood-Test Barrier:

  • Separates the seminiferous tubule into basal and adluminal compartments
  • Made of tight junctions to prevent paracellular transport
  • Prevents entry of noxious chemicals and autoimmune responses
  • Physiological disruption related to spermiation and feedback mechanisms
• Gene Transcription During Spermatogenesis:
• Transcription at diplotene:

  • Y chromosome of Drosophila transcribed for sperm viability
  • Isoform for B tubulin necessary for sperm motility
  • mRNA for bindin transcribed late in spermatogenesis for binding of sperm and egg
  • Akap82 transcribed at spermatid stage
  • mRNA for sperm protamine protein transcribed by spermatid for compacting chromatin
• Hormonal Control of Spermatogenesis:

  • Spermatogenesis at puberty depends on the hypothalamus, pituitary, and gonadal axis to produce testosterone
  • FSH is crucial for the secretion of ABP and development of the blood-testis barrier
  • Sperm yield increases with FSH, preventing atresia of Type A spermatogonia
  • Sexual activity affects FSH levels and inhibin decreases FSH
• Oogenesis:

  • Differs from spermatogenesis in various aspects including product cell motility, size, and genetic composition
  • Oogenesis involves meiotic arrests and the production of a single functional ovum
  • Primordial germ cells have different fates leading to the development of oocytes or spermatogonia
• Yolk is present in the eggs of all animals except mammals
• Mammals do not have yolk in their eggs because they do not produce a significant amount of mRNA
• Yolk was discovered in the late 19th Century in the eggs of an amphibian and a fish
• Yolk distributes in a specific manner in the oocyte, with ribosomes, mitochondria, platelets, and little cytoplasm found in the animal pole, and a large amount of yolk in the vegetal pole
• Animal/vegetal axis is established with yolk platelets in vegetal hemispheres and glycogen granules, lipid inclusions, ER, and ribosomes in the animal pole
• Specific RNAs are localized to certain regions of the cytoplasm, credited to the cytoskeleton
• Oocytes produce transcripts for themselves and the future zygote, which should be sequestered from others and not translated unless fertilized
• Cortical granules found in the actin-rich cortex are important during fertilization to prevent polyspermy and ensure only one sperm fertilizes the egg
• Specific localizations are important for development and differentiation, as proven by centrifugation experiments
• MPF (Maturation Promoting Factor) drives cells to enter mitosis and is regulated by cyclin-dependent kinase molecules
• LH (Luteinizing Hormone) triggers ovulation and is the stimulus for the continuation of meiosis
• Ovulation patterns in mammals vary, with eggs ovulated during sexual intercourse in MII (meiosis II) stage
• Hormonal regulation of ovulation starts with environmental cues and involves the growth of follicles and initiation of ovulation