Prenatal Development Stages and Gamete Formation

• Prenatal development occurs in three periods:

  • Germinal period (weeks 1-2): Formation of primitive germ layers.
  • Embryonic period (weeks 3-8): Development of organ systems.
  • Fetal period (weeks 9-38): Growth and maturation of organ systems.

• Clinical age uses the mother's last menstrual period (LMP) to calculate the age of the unborn child.

• Postovulatory age is 14 days less than clinical age, and ultrasound can verify embryo status to estimate the due date if menstrual periods are irregular.

Embryonic Origin of Gametes

• Primordial germ cells (PGCs) arise from epiblast during the 2nd week to form gametes.
• Gametes migrate to the wall of the yolk sac before embryo development to gain nutrients.
• PGCs migrate from the yolk sac to the wall of the gut tube/hindgut, then to the dorsal body wall in weeks 4-6.
• PGCs populate the body wall region by mitosis at the level that will form the gonads (organs that produce gametes).

Meiosis

• Meiosis requires two cell divisions.
• Meiosis I:
  • Male and female germ cells replicate their DNA, duplicating each of the 46 chromosomes into sister chromatids.
  • Homologous chromosomes align in pairs during synapsis.
  • Chiasma via "crossing over" contributes to genetic variation.
  • Chromosomes are separated into two daughter cells, reducing chromosome number from diploid to haploid.
• Meiosis II:
  • Separates sister chromatids.
  • Four daughter (haploid) cells are obtained, and each gamete contains 23 chromosomes.

Gametogenesis

• Male gametogenesis: PGCs remain dormant until puberty, then undergo meiosis and differentiate into spermatozoa.
• Female gametogenesis: Remains as a primary oocyte until puberty, then continues/completes meiosis to become an oocyte.
• Major events in gametogenesis:
  • Extraembryonic origination of germ cells (posterior epiblast precursors/mesoderm) and their migration into the gonads.
  • Increase in germ cell number by mitosis.
  • Chromosomal number reduction by meiosis to become haploid.
  • Structural and functional maturation of eggs and spermatozoa.

Male Gametogenesis

• PGCs remain dormant from the 6th week of embryonic development until puberty.
• At puberty, PGCs in seminiferous tubules differentiate into spermatogonia.
• Spermatogonia undergo meiosis and mature into spermatozoa in successive waves.
• Stages of meiosis in males:
  • Spermatogonia
  • Primary spermatocytes
  • Secondary spermatocytes
  • Spermatids
  • Spermatozoa
• Spermiogenesis is the transformation of haploid round spermatids into streamlined spermatozoa capable of motility.
  1. Formation of the acrosome (contains enzymes for egg penetration).
  2. Condensation of the nucleus.
  3. Formation of the neck and middle piece (mitochondria for energy) and tail.
  4. Shedding of cytoplasm as residual bodies for streamlined shape.
• Spermatozoa are continuously produced from puberty until death.

Female Gametogenesis

• Primary follicle/oocyte: Follicle cells around the oocyte become more cuboidal, zona pellucida (protein layer) forms.
• Secondary follicle: A cavity called the follicular antrum forms; the oocyte starts the first meiotic division.
• Graafian follicle: The antrum enlarges, the oocyte is pushed to the periphery, and it starts the second meiotic division.
• The cell enters meiosis II but arrests in metaphase approximately 3 hours before ovulation.
• Meiosis II is only completed if the oocyte is fertilized.
• The cell degenerates approximately 24 hours after ovulation if unfertilized.

Fertilization

• Ampulla foldings consist of simple columnar ciliated epithelium to facilitate oocyte movement.
• Peg cells secrete nutrients to nourish the oocyte.
• Oocyte penetration by a spermatozoon:
  • Penetration of the corona radiata.
  • Penetration of the zona pellucida.
  • Fusion of the cell membrane.
• Genetic materials from a haploid sperm cell and haploid secondary oocyte merge into a single diploid nucleus, restoring diploidy.
• Fertilization happens within 24 hours of ovulation in the ampulla.
• Response of the egg to prevent polyspermy (only one sperm enters):
  • CORTICAL REACTION: Oocyte releases cortical granules (lysosomal enzymes) onto its surface by exocytosis.
  • ZONA REACTION: The zona pellucida alters its structure and composition to prevent sperm binding and penetration.
• Fertilization stimulates the penetrated oocyte to complete meiotic II division.

Cleavage

• Cleavage is the cell division (mitosis) with little to no growth in the early embryo.
• The zygote is subdivided into many smaller daughter cells called blastomeres.
• Importance of cleavage:
  • Restores the normal cytoplasm:nucleus ratio.
  • Transcription and protein synthesis activation.
  • Maternal recognition of pregnancy (prevents immune system targeting the zygote, by secreting several hormones such as HCG).
  • Cell fate determination.
• Morula: Tight junctions develop between cells, enabling blastomeres to become more compact within the zona pellucida.

Compaction

• Compaction is the process of forming tight junctions.
• Cell-to-cell contacts are maximized after compaction.

Blastogenesis/Blastocyst Formation

• Day 1: Oocyte becomes fertilized in the ampulla.
• First 5 days: The zygote undergoes cleavage as it travels down the oviduct and enters the uterus.
  • Monozygotic twinning typically occurs during cleavage/blastocyst stages.
  • Monozygotic twin: Arises from fertilization of one egg by one sperm.
  • Cleavage of an early embryo forms two blastocysts and each half develops as a separate embryo.
  • Splitting of the inner cell mass of the blastocyst forms two embryos enclosed in a common trophoblast, bound by a single amniotic cavity.
  • Incomplete separation of inner cell mass results in conjoined twins.
• Day 5: The blastocyst hatches from the zona pellucida just before implantation.
  • Inability to hatch results in infertility and premature hatching may result in abnormal implantation in the uterine tube.
• Day 6: The blastocyst implants in the uterine endometrium.
  • Trophoblast cells at the embryonic pole of the blastocyst penetrate the uterine mucosa.
  • Syncytiotrophoblast actively invades the endometrium of the uterus.
  • Ectopic implantation: Implantation occurs in oviducts/abdominal cavities.
  • Tubal pregnancies are the most common type of ectopic pregnancy.
  • Most tubal pregnancies are in the ampullary portion of the tube, but can be located anywhere from the fimbriated end to the utero-tubal junction.
  • Rupture can lead to life-threatening hemorrhage.

Summary of the 1st week of development

• Major events:
  1. Fusion of male and female gametes
  2. Mitotic divisions increases the number of cells = blastomeres.
  3. Development of blastocyst with inner and outer cell mass formation.
  4. Attachment of blastocyst onto the endometria of the uterus.
• Main structural stages:
  • Zygote: Divides to form 2 cells about 18-39 hours after fertilization.
  • Morula: Solid ball of cells (blastomere) with zona pellucida.
  • Blastocyst: Hollow sphere of cells and starts to burrow into the uterine wall, trophoblast cells develop into the placenta.