Gametogenesis Flashcards

Gametogenesis Learning Objectives

• Describe the phases of gametogenesis in chronological order and identify where in the embryo they occur.
• Describe the migration route of primordial germ cells, and what happens when there is an error in migration.
• Compare and contrast male and female gametogenesis.
• Summarize the hormones, tissues, and cells responsible for regulating spermatogenesis.
• Describe the structure of a seminiferous tubule. How does a cell's position within the tubule relate to its identity?
• Explain how sperm mature. What subcellular changes occur within a sperm cell during maturation?
• Discuss this statement: abnormal sperm are normal. Is this statement supported? Why or why not?

Overview of Gametogenesis

• Gametogenesis is the formation of gametes (sperm and eggs).
• It's the process where a diploid (2n/2c) cell undergoes meiosis to form haploid (1n/1c) gametes.
• The term 2n/2c refers to diploid cells, with "2n" indicating that the cell has two sets of chromosomes (one from each parent), and "2c" indicating that each of these chromosomes consists of two sister chromatids (after DNA replication).
• The term 1n/1c refers to haploid cells, with "1n" indicating that the cell has a single set of chromosomes, and "1c" indicating that each of these chromosomes consists of a single chromatid (i.e., they are unreplicated).

Phases of Gametogenesis:

1. Primordial germ cells (PGCs) form in extraembryonic tissue and migrate to the gonad.
2. Germ cell number increases by mitosis.
3. Chromosome number is reduced by meiosis.
4. Maturation of eggs and sperm.

• There is overlap between phases 1 & 2, as PGCs are dividing as they migrate.

Primordial Germ Cells (PGCs)

• PGCs are the cell lineage that becomes the gametes.
• They form very early in development.
• In humans, PGCs are seen in the wall of the yolk sac by Week 4.
• PGCs migrate from the yolk sac towards the mesonephros (early kidney) at the posterior body wall and settle in the genital ridge (PGCs + genital ridge becomes the gonad).
• The PGCs are dividing as they migrate; in the mouse, approximately 100 cells leave the yolk sac, and approximately 4000 cells enter the genital ridge.
• They migrate together as a group.
• The germ cells and the genital ridge depend on each other for proper development.
• Absence or failure of either leads to abnormal development of the gonad.
• Germ cells induce genital ridge development.
• The genital ridge induces germ cell development.
• Primordial germ cells: before reaching the gonad.
• Germ cells: once in the gonad. The terms can be used interchangeably.

Timing of Germ Cell Development

• The timing is different in males and females.

Males:

• PGCs remain as PGCs and are dormant until puberty.
• During puberty, PGCs differentiate into spermatogonia.
• Spermatogonia produce sperm via meiosis.
• Once spermatogenesis begins in the male, it continues until death.
• Elderly men can father children; however, there is an increased risk of some birth defects in children of older men.

Females:

• PGCs increase their number by mitosis, differentiate into oogonia, and begin meiosis during embryonic development.
• They become stalled in meiotic arrest (prophase of meiosis I) as 1o oocytes and remain stuck in meiosis I until puberty.
• Hormonal changes at puberty cause a few oocytes per month to resume meiosis, and one oocyte each month to mature and be ovulated.
• These cycles continue until menopause at approximately 50 years of age.
• Menopause limits a woman’s reproductive abilities but can be overcome by in vitro fertilization (IVF).
• Erramatti Mangamma is believed to be the world’s oldest mother, giving birth to twins in September 2019 at age 74 using IVF treatments and a donor egg.
• Elderly fathers are much more common than elderly mothers.

Germ Cell Tumors (Teratomas)

• Occasionally, a primordial germ cell gets lost during migration and forms a germ cell tumor called a teratoma.
• Since germ cells are pluripotent, these tumors have a very broad range of tissue phenotypes, even fully differentiated structures like hair, teeth, and brain.

Hormones and Tissues Controlling Spermatogenesis

• At puberty in the male, the testes begin to secrete the steroid hormone testosterone.
• This is triggered by a cascade of hormones, originating from the brain:
  • The hypothalamus produces GnRH (gonadotropin-releasing hormone).
  • GnRH instructs the pituitary to produce LH (luteinizing hormone) and FSH (follicle-stimulating hormone).
  • The Leydig (interstitial) cells of the testis respond to LH by producing testosterone (T).
  • The Sertoli cells respond to FSH (and also T) and initiate spermatogenesis.
• Testosterone triggers male primary and secondary sex traits:
  • Primary sex traits: testes development, spermatogenesis
  • Secondary sex traits: facial hair, muscle development, deepening of the voice

Spermatogonia Development

• Testosterone induces dormant PGCs, now in the seminiferous tubules of the testis, to divide by mitosis and become spermatogonia.
• PGCs differentiate into spermatogonia, which are stem cells.
• Spermatogonia remain present and actively dividing throughout the male lifespan.
• Spermatogonia divide by mitosis to produce more of themselves (stem cells) OR differentiate to become 1o spermatocytes, which enter meiosis.
• 1o spermatocytes complete meiosis I to make 2o spermatocytes.
• 2o spermatocytes complete meiosis II to make spermatids.
• 2o spermatocytes are the last cell type to divide. The spermatids undergo maturation (spermiogenesis) but are not replicating.

Sperm Development

• During sperm development, cells move from the basal surface of the seminiferous tubule to the lumen.
• The developing sperm exist in a syncytia with each other and the Sertoli cells.
• Sertoli cells are large complex cells that provide structure and nourish the developing sperm.
• All the cells are joined by cytoplasmic bridges and can exchange materials; this results from incomplete cytokinesis during mitosis.
• Spermatogenesis involves two meiotic divisions as the cells move inward.
• Primary spermatocytes are diploid (2 copies of each chromosome).
• The first division of the 1o spermatocyte (Meiosis I) yields two haploid 2o spermatocytes.
• The second division (Meiosis II) yields 4 haploid spermatids.

Spermiogenesis

• Spermiogenesis is the process of spermatids becoming mature sperm.

1. Removal of most of the cytoplasm from the spermatids via cytoplasmic bridges with Sertoli cells that draw it out.
2. DNA of the sperm becomes highly condensed, and histone proteins are replaced with protamines, which allow tight packing of DNA into the sperm head.
3. Addition of the tail and other morphological changes.

• Spermiation is the final step and breaks down the interconnections between the sperm and Sertoli cells, releasing mature spermatozoa into the lumen.
• The mature sperm contains a head, midpiece, and long tail:
  • Head: tightly packaged DNA and a vesicle of hydrolytic enzymes called the acrosome at the tip that is used for penetrating the egg.
    • The acrosome is derived from the Golgi apparatus of the cell.
  • Midpiece: mitochondria that generate the energy for swimming to the egg.
  • Tail: flagellum used for propulsion while swimming.

Sperm Movement and Maturation

• After production, sperm move to the epididymis for storage.
• Upon ejaculation, they move through the vas deferens and mix with secretions from the seminal vesicle and prostate glands, and this mixture is semen.
• After ejaculation, sperm remain viable and capable of fertilization for approximately 3 days.
• Capacitation is the final step of sperm development that occurs within the female reproductive tract and only occurs in mammals.
  • It readies the acrosome to release its enzymes upon encountering the egg.
  • Sperm used for in vitro fertilization must be artificially capacitated or injected into the egg (intracytoplasmic sperm injection (ICSI)).

Sperm Production and Abnormalities

• Sperm are generated in huge numbers, approximately 100 million per day, every day throughout the human male lifespan.
• Approximately 200 million sperm are present in any one human ejaculate.
• Only a few hundred may reach the egg because most die or are killed along the way.
• Each cycle of spermatogenesis takes about 74 days in the human, or 3 months if you include maturation time in the epididymis.
• Abnormalities in sperm development mean that many will develop grossly abnormally.
• In a typical semen sample, you will see sperm with 2 heads, 2 tails, no tail, uncompacted chromatin, etc.
• Abnormal sperm are usually so compromised in their ability to swim or penetrate the egg that they aren’t fertile.
• Using strict morphology criteria, only 4-14% of sperm are “normal”.
  • This number varies by lab and depends on what criteria are used.
• Analyses of sperm quality do not depend solely on morphology; they also include:
  • Semen volume
  • Total number of sperm
  • Concentration of sperm
  • Motility of sperm (% moving normally)
  • Viability of sperm (% alive)
• Men with abnormally low sperm quality are not necessarily incapable of having children.
• However, they may have more trouble conceiving.
• Sperm morphology varies highly between species.
• Having abnormal sperm is normal.