Embryology and Development: 1-3WEEKS

• Gametogenesis is the development of gametes.

Spermatogenesis

• Spermatogenesis is the development of spermatids from primordial germ cells, leading to spermatozoa, under the influence of anterior pituitary gonadotropic hormones.
• Spermatogenesis includes:
  • Multiplication: Primordial germ cells multiply via mitosis, creating spermatogonia in males.
  • Growth: Spermatogonia grow into primary spermatocytes.
  • Maturation: Primary spermatocytes undergo two meiotic divisions, resulting in spermatids (four per primary spermatocyte).
• Spermatogonia undergo significant growth and are arrested in prophase of the first meiotic division for 16 days becoming primary spermatocytes.
• Primary spermatocytes contain 22 pairs of autosomes and one pair of sex chromosomes (XY).
• Primary spermatocytes divide into secondary spermatocytes, each containing either 22+X or 22+Y chromosomes.
• Further division leads to the formation of four spermatids, each with haploid chromosomes (23X and 23Y).
• Morphological abnormalities include:
  • Giants, dwarfs, or fused sperm, which often lack motility.
• Numerical abnormalities include:
  • Oligospermia: Low sperm count in semen.
  • Aspermia: Absence of sperm in semen.
  • Necrospermia: Presence of dead sperm in semen.

Oogenesis

• Oogenesis is the development of germ cells (oogonia) into mature oocytes.
• Primordial Germ Cells (PGCs) form in the epiblast during the second week of embryonic development, migrating to the yolk sac and then to the gonads by week five.
• At five weeks, gonadal ridges form, differentiating into ovaries for XX embryos and testes for XY embryos.
• Oocyte maturation begins during fetal development, accelerates at puberty, and concludes at menopause.
• Germ cell numbers peak at 7 million in the ovaries by the fifth month, with cell death (atresia) causing significant loss by the seventh month.
• At birth, females have between 600,000 and 800,000 primary oocytes, arrested in the diplotene stage of prophase I due to OMI secreted by follicular cells.
• By puberty, the number of primary oocytes drops to about 40,000.
• The ovarian cycle is initiated by rising FSH levels, leading to the ovulation of fewer than 500 oocytes over a female’s reproductive life.
• The follicular stages include:
  • Primary Follicle: Granulosa cells form layers around the primary oocyte, establishing the zona pellucida.
  • Secondary Follicle: Follicles mature, forming layers of granulosa cells and developing an antrum, reaching a diameter of 25mm at maturity.
  • Tertiary Follicle: Lasts approximately 37 hours preovulation, spanning the width of the ovarian cortex with a large antral cavity.
• A surge in luteinizing hormone (LH) triggers completion of the first meiotic division, dividing the primary oocyte into a secondary oocyte and a polar body.
• The maternal contribution to the oocyte includes:
  • Half of the zygotic genome.
  • Maternal mitochondria for energy production.
  • Maternal nucleolus for ribosome synthesis.
  • Maternal ribosomes for protein production.
• The paternal contribution to the oocyte includes:
  • Half of the zygotic genome.
  • A centriole for cell division.
• The female reproductive cycle begins at puberty and continues until menopause.
• The ovarian cycle begins around ages 11-14 and concludes between 45-50 years, regulated by FSH and LH from the anterior pituitary gland.
• These hormones induce cyclic changes in the ovaries, leading to:
  • Development of ovarian follicles.
  • Ovulation.
  • Formation of the corpus luteum.
• Follicular development includes:
  • Growth and differentiation of the primary oocyte.
  • Proliferation of follicular cells.
  • Formation of the Zona Pellucida around the oocyte.
  • Development of the Theca Folliculi.
• Ovulation occurs mid-cycle (around day 14 in a 28-day cycle), driven by FSH and LH, resulting in a bulge on the ovarian surface.
• Key phenomena during ovulation include:
  • An avascular spot (Stigma) appears on the bulging follicle.
  • Fimbriae of the uterine tube sweep over the ovary, facilitating oocyte transport.
• The collapsed walls of the ovarian follicle form the corpus luteum post-ovulation.
• It secretes progesterone and lesser amounts of estrogen, preparing the endometrium for potential implantation.
• If fertilization occurs, the corpus luteum enlarges and remains active for about 20 weeks.
• If fertilization does not occur, the corpus luteum degenerates within 10-12 days.
• The uterine cycle corresponds to oocyte maturation, ovulation, and entry into the uterine tube, marked by endometrial changes influenced by estrogen and progesterone.
• The average menstrual cycle lasts 28 days, varying between 23 and 35 days in 90% of women.
• The phases of the menstrual cycle are:
  • Menstrual Phase: Begins with menstrual flow.
  • Proliferative Phase: Endometrial thickening.
  • Luteal Phase: Hormone secretion from the corpus luteum.
  • Ischemic Phase: Occurs if fertilization does not take place.
• If Fertilization Occurs:
  • The fertilized ovum implants in the endometrium around the sixth day of the luteal phase.
  • Human chorionic gonadotropin (HCG), secreted by the syncytiotrophoblast, sustains the corpus luteum, preventing menstruation.
• If Fertilization Does Not Occur:
  • The corpus luteum degenerates without HCG, causing a decline in estrogen and progesterone levels, leading to menstruation.
• In pregnancy, the endometrium transitions into the pregnancy phase, with menstruation resuming 6-10 weeks after childbirth.
• Sperm must undergo capacitation before fertilization to penetrate the egg.
• After fertilization, the zygote is formed, characterized by two polar bodies, two pronuclei, and an initial diameter of 0.1 mm.
• Cleavage involves cell divisions of the zygote every 12-24 hours without growth, maintaining a diameter of approximately 100 µm.
• Cleavage initiates around 24 hours post-fertilization.
• The first two-cell stage yields blastomeres that are equivalent and totipotent.
• Subsequent cleavages result in four and eight cell stages, still contained within the zona pellucida.

Implantation

• The blastocyst burrows into the uterine lining (endometrium).
• The trophoblast differentiates into:
  • Syncytiotrophoblast: A multinucleated layer invading the endometrium, facilitating implantation and nutrient exchange.
    • Invasive fused cells (syncytium) derived from cytotrophoblast.
    • Breaks maternal capillaries, trophoblastic lacunae fill with maternal blood.
  • Cytotrophoblast: A layer of mononucleated cells beneath the syncytiotrophoblast (stem cell population).
• The inner cell mass differentiates into:
  • Epiblast: Dorsal layer of high-columnar cells towards the amnion, giving rise to the ectoderm, mesoderm, and endoderm. It contributes to forming the overlying amniotic membrane and amniotic cavity.
  • Hypoblast: Ventral layer of low-cuboidal cells towards the blastocyst cavity, forming the yolk sac.
• By the bilaminar disc formation several extraembryonic membranes start to develop:
  • Amnion:
    • A fluid-filled sac that surrounds and protects the embryo.
    • Formed by a space b/w ectoderm and trophoblast
      • Floor=ectoderm
      • Roof=amniogenic cells which secrete amniotic fluid
  • Yolk Sac:
    • A sac that provides early nourishment to the embryo.
    • Flat cells originate from the endoderm, form a membrane called exocoelomic membrane which lines the blastocyst cavity
      • Now called Exocoelomic cavity
      • This alongside membrane = primary yolk sacs
  • Chorion:
    • The outermost membrane
    • This will eventually contribute to the placenta.
  • By day 13, proliferation of Cytotrophoblast cells produce extensions inside Syncytiotrophoblast to form primary chorionic villi.
• Endometrial cells undergo apoptosis to facilitate invasion by the Syncytiotrophoblast.
• This engulfs degenerating cells for embryo nutrition.
• Implantation can be detected by:
  • Ultrasonography.
  • hCG (human chorionic gonadotropin secreted by the Syncytiotrophoblast) near the end of the 2nd week.
  • Blood-filled Lacunae appear in the Syncytiotrophoblast, forming a network by day 10 or 11.
• The Syncytiotrophoblast:
  • Erodes the endothelial lining of maternal capillaries, known as sinusoids.
  • Maternal capillaries' blood reaches the lacunae, establishing uteroplacental circulation by day 11 or 12.

Gastrulation

• Gastrulation is when the two-layered epiblast transitions into three primary embryonic germ layers: ectoderm, mesoderm, and endoderm, establishing axial orientation.
• Ectoderm develops into the epidermis, central and peripheral nervous systems, eyes, and internal ears; neural crest cells contribute to connective tissues in the head.
• Endoderm forms the epithelial lining of the respiratory and alimentary tracts, including associated glands like the liver and pancreas.
• Mesoderm is responsible for skeletal muscles, blood cells, linings of blood vessels, and connective tissues (cartilage, bones, tendons, and ligaments).
• The notochord begins to form from axial mesoderm migrating along the midline through the primitive node.
• The paraxial mesoderm generates around 35 pairs of somites, differentiating into:
  • Sclerotome: Forms cartilage and bone.
  • Myotome: Develops into muscles.
  • Dermatome: Gives rise to the dermis of the skin.
• The lateral plate mesoderm differentiates into:
  • Somatopleure: Producing voluntary muscles and the parietal layers of pleura and peritoneum.
  • Splanchnopleure: Giving rise to involuntary muscles of the heart and the lining of the gut.
• The development of the cardiovascular system occurs alongside somite formation.
• The intraembryonic coelom forms between the somatopleure and splanchnopleure
• It further facilitates the development of body cavities and their linings.
• The third week is highly sensitive, and disturbances can lead to developmental issues.
• Sacrococcygeal Teratoma:
  • The most common tumor in newborns.
  • Incidence is approximately 1 in 35,000.
  • Predominantly affects females (80%).
  • Diagnosed via routine ultrasonography and generally has a good prognosis post-surgery.
• Caudal Agenesis (Sirenomelia):
  • Insufficient gastrulation leads to this condition.
  • Marked by premature regression of the primitive streak, resulting in the loss of trunk and lower limb mesoderm.
  • Associated anomalies include the VATeR association (vertebral defects, anal atresia, tracheo-esophageal fistula, renal defects) and the VACTeRL

The Allantois

• Appears as a finger-like diverticulum from the caudal wall of the yolk sac on day 16.
• It remains relatively small in the human embryo but serves essential functions related to blood formation and the development of the urinary bladder.
• Allantoic cysts are remnants of the allantois that can occur between the fetal umbilical vessels.
• These cysts are typically asymptomatic until childhood or adolescence and may become infected or inflamed.

Fate of the Axial Mesoderm

• The notochord and pre-chordal plate arise from mesodermal cells migrating cranially along the midline after passing through the embryonic node.
• Both structures serve as signaling centers, orchestrating the patterning of the overlying ectoderm and underlying endoderm.

Functions of the Notochord

• Contributes to the formation of the axial skeleton, including the bones of the head and vertebral column.
• Induces the overlying ectoderm to thicken to form the neural plate.
• Degenerates as the vertebrae develop, leaving behind the nucleus pulposus of the intervertebral discs.
• Initiates signaling events that transform unspecialized embryonic cells into defined tissues and organs.

Development of Somites and Cardiovascular System

• Somite formation is a critical transition in embryonic development, marking the segmentation of the body plan and formation of the vertebral column (Days 19-21).
• By the end of the second week, embryonic nutrition shifts to maternal blood supply through diffusion via the extraembryonic coelom and the umbilical vesicle.
• The first blood cells arise in the yolk sac.

Vasculogenesis and Angiogenesis

• Vasculogenesis refers to forming new vascular channels through the assembly of angioblasts.
• Angiogenesis involves forming new vessels by budding and branching from preexisting vasculature.
• Blood vessels begin to form approximately two days after the onset of the third week, correlating with the urgent need for oxygen and nutrients from maternal circulation.

Development of the Trophoblast

• Trophoblast consists of primary villi formed from the cytotrophoblast, which is covered by syncytiotrophoblast.
• As mesodermal cells invade these villi, they become secondary villi.
• The formation of small blood vessels within these villi leads to the creation of tertiary villi
• The trophoblast is then referred to as the chorion.
• Nutritional Support: Free villi facilitate the nutrition of the embryo.
• Anchoring: Anchoring villi fix the embryo in place.
• Respiration: They play a role in the respiratory exchange for the embryo.
• Excretion: Villi assist in the excretion of waste products.

Test your knowledge of early human development, from fertilization through gastrulation. This includes zygote formation, blastomere characteristics, trophoblast function, and germ layer origins. Also covers spermatogenesis and related topics.