Early human development (weeks 1-4)

Fertilization: entrance of a sperm cell into an egg. Must occur within 24-48 hours of ovulation if Fertilizationampulla of a uterine tube.

  1. Cell motility
    1. Sperm rely on flagellum; producing whipping movements via ATP hydrolysis that “propels” the sperm to the fallopian tubes.
    2. Relies on structural proteins tubulin-microtubules & interaction w/ motor protein, dynein
  2. Plasma membrane fusion
    1. Changing fluidity and structure of the sperm and egg membranes
      1. Binds to the outer layer and then attempts to penetrate the hard zona pellucida
      2. Upon reaching the corona radiate layer of the egg, the acrosome, a cap-like structure at the tip of each sperm, releases the enzyme hyaluronidase, which breaks down the hyaluronic acid contained in the presenting egg layer
  • Acorosome contains lytic enzymes—trypsin-like protease Acrosin (promotes changes in the structure and fluidity of the membranes of the sperm tip and the egg to cause them to fuse). Acrosin facilitates, but not required to penetrate zona pellucida.
  1. Following initial fusion, a protein molecule on the sperm acrosome binds to a directly interlocking protein, ZP3, on the egg
  2. This binding is believed to initiate a series of reactions, included the acrosome reaction, a release of enzymes by the acrosome, which complete the membrane fusion; the cortical reaction; and activation of the egg to undergo a second meiotic division
    1. Cortical reaction: considered the analogous process to the acrosome reaction
    2. Binding of sperm to egg results in a release of Ca2+ ions, which promote fusion of cortical granule membranes with the egg’s plasma membrane
    3. Fusion expresses factors that cause the release of an externally bound, membrane protein on the outer vitelline layer of the egg
    4. Release of this protein forces the vitelline layer away from the zona pellucida, moving any other sperm away permanently and inhibiting any other sperm from fertilizing the egg
    5. The polysaccharide molecule hyalin is also released from the cortical granules to create a layer aroujnd the egg that also impedes any further fertilization
  3. Fusion of sperm and secondary oocyte cell membrane. Fusion to the ovum membrane is mediated by fertilin, a protein on the surface of the sperm head. The entire sperm enter the membrane of the secondary oocyte. The tail and the mitochondria of the sperm degenerate (that’s why all mitochondria of zygote is maternal). The oocyte completes meiosis II forming a mature ovum and a second polar body The male and female nucleoli fuse, forming a zygote (diploid, 46 chromosomes). The zygote’s sex is determined at fertilization by the kind of the fertilizing sperm.

Implantation:

  1. Takes place into the uterine wall 6 or 7 days after fertilization
  2. Process driven by the cells of the trophoblast
  3. Can be divided into 3 phases and lasts approximately 3 days:
    1. Apposition: initial adhesion of the blastocyst to the uterine wall; most commonly occurs on the upper posterior uterine wall; blastocyst is composed of 100 to 250 cells
    2. Adhesion: increased physical contact between the blastocyst and uterine epithelium
    3. Invasion: penetration & invasion of syncytiotrophoblast and cytotrophoblast into the endometrium, inner 3rd of the myometrium, and uterine vasculature.
      Cytotrophoblast is a mitotically active inner layer of the trophoblast that migrates to the syncytiotrophoblast and they fuse and lose their cell membranes. Syncytiotrophoblast is a rapidly expanding multinucleated mass that invades the endometrial tissues and helps the blastocyst become embedded in the endometrium. Then the syncytiotroblastic cells displace the endometrial cells at the implantation site while the endometrial cells undergo apoptosis to facilitate invasion.
  4. Endometrium must be appropriately primed with estrogen and progesterone for successful implantation; limited to days 20-24 of the cycle; process mediated by cell surface receptors
  5. Successful endometrial blastocyst adhesion involves modification in expression of cellular adhesion molecules (CAMs)
  6. The integrins – one of four families of CAMs – are cell-surface receptors that mediate adhesion of cells to extracellular matrix proteins
  7. Endometrial integrins are hormonally regulated, and a specific set of integrins expressed at implantation
  8. The syncytiotrophoblast produces enough HCG at the end of the second week to give a positive pregnancy test
  9. Molecular mechanisms of implantation: involve synchronization between the invading blastocyst and a receptive endometrium. The microvilli of endometrial cells, cell adhesion molecules (integrins), cytokines, prostaglandins, hormones (hCG and progesterone) growth factors, and extracellular matrix and enzymes (matrix metalloproteinase and protein kinase A) all play a role in making the endometrium receptive.The connective tissue cells around the implantation site accumulate glycogen and lipids.

Placentation

  1. The trophoblast (see above) plays a crucial role at the fetal-maternal interface; differentiates into an outer miultinucleated syncytiotrophoblast, and an inner layer of primitive mononuclear cells: cytotrophoblast
  2. The invading syncytiotrophoblast surrounds small islands of endometrium that contain blood vessels
  3. Enzymes secreted by the syncytiotrophoblast lyse the maternal tissue, leaving spaces, or lacunae, and rupturing blood vessels; the ruptured vessels fill the syncytiotrophoblast-lined lacunae with maternal blood
  4. Solid cords of chorionic tissue (chorionic villi) grow into these lacunae; these cords bring the blood in the fetal vessels close enough to the maternal blood in the lacunae for exchange to occur and also form a selectively permeable placental barrier
  5. Primary villi are tongues of syncytiotrophoblast and cytotrophoblast
  6. The underlying extraembryonic mesenchyme invades the primary villi to form secondary villi, composed of syncytiotrophoblast, cytotrophoblast, and a core of extraembryonic mesenchyme
  7. The extraembryonic mesenchyme differentiates into blood vessels that later connect with the umbilical vessels of the fetus.
  8. Tertiary villiare thus composed of syncytiotrophoblast, cytotrophoblast, and extraembryonic mesenchyme that contains blood vessels in its core
  9. The cytotrophoblast gradually disappears as its cells fuse with the syncytiotrophoblast.

Primary germ layer formation (and their derivatives)

  1. Three layers: ectoderm, mesoderm, and endoderm; termed “gastrulation” and give rise to the primordial of all the tissues and organs.
  2. Derivatives follow:
    1. Ectoderm: central nervous system, peripheral nervous system; sensory epithelia of the eyes, ears, and nose; epidermis and its appendages (hair and nails); mammary glands; pituitary gland; subcutaneous glands; and enamel of teeth.
      1. Neural crest cells: derived from neuroectoderm and give rise to the cells of the spinal, cranial nerves, and autonomic ganglia; ensheathing cells of the peripheral nervous system; pigment cells of the dermis
    2. Mesoderm: connective tissue; cartilage; bone; striated and smooth muscles; heart, blood, and lymphatic vessels; kidneys, ovaries; testes; genital ducts; serous membranes lining the body cavities (pericardial, pleural, and peritoneal); spleen; and cortex of suprarenal glands
  • Endoderm: epithelial lining of the digestive and respiratory tracts, parenchyma of the tonsils, thyroid and parathyroid glands, thymus, liver, and pancreas.
  • Mark Hanks

    Interesting topic, thanks for sharing