Lecture 9: Reproduction - male embryonic and postnatal

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Questions and Answers

What are the two primary fates of spermatogonia cells?

  • Self-renewal or sperm maturation
  • Self-renewal or spermatogenesis (correct)
  • Mitosis or meiosis
  • Cell death or differentiation

What technique was primarily used to demonstrate the repopulation of testes by SSCs?

  • Flow cytometry analysis
  • LacZ+ gene labeling (correct)
  • CRISPR gene editing
  • Gene knockout therapy

Which of the following results confirmed that LacZ+ SSCs contributed to normal spermatogenesis in recipient mice?

  • Presence of spermatogonia in the seminiferous tubules
  • Increased testis size and weight
  • Clear staining for β-galactosidase in the testes (correct)
  • Complete absence of germ cells in recipients

What does the detection of β-galactosidase activity indicate in this study?

<p>Successful repopulation of the testis by SSCs (A)</p> Signup and view all the answers

What was the condition of the recipient mice's testis before the injection of LacZ+ SSCs?

<p>Depleted of their own germ cells (D)</p> Signup and view all the answers

What is the primary process that occurs in spermatogonial stem cells during the embryonic stage?

<p>Self-renewal (D)</p> Signup and view all the answers

At which stage does spermatogenic activity first begin to activate?

<p>Puberty (C)</p> Signup and view all the answers

During adulthood, how is spermatogenesis characterized?

<p>It is a continuous process with daily sperm production. (B)</p> Signup and view all the answers

What happens to one daughter cell during the mitotic division of spermatogonial stem cells at puberty?

<p>It maintains the stem cell population. (C)</p> Signup and view all the answers

What is the main outcome of sperm maturation in the epididymis?

<p>Development of motility and fertilization capability. (D)</p> Signup and view all the answers

What occurs during childhood regarding the spermatogonial population?

<p>Spermatogonia proliferate without active spermatogenesis. (B)</p> Signup and view all the answers

Which phase of sperm development follows the completion of meiosis?

<p>Spermiogenesis (D)</p> Signup and view all the answers

What is the key feature of spermatogenic activity during the childhood stage?

<p>Presence of spermatogonia without spermatogenesis. (B)</p> Signup and view all the answers

What is the fate of the spermatogonia during the embryonic stage before puberty?

<p>They solely undergo self-renewal. (D)</p> Signup and view all the answers

What is the primary distinction between germline stem cells and multipotent stem cells?

<p>Germline stem cells are unipotent and only produce germ cells, whereas multipotent stem cells can differentiate into various cell types. (B)</p> Signup and view all the answers

What characterizes a terminally differentiated germ cell?

<p>It has irreversibly lost its ability to proliferate and has reached its final stage of development. (D)</p> Signup and view all the answers

Why is the genomic quality of differentiated germ cells significant?

<p>It carries the DNA that may lead to potential genetic disorders in the offspring. (C)</p> Signup and view all the answers

What type of stem cells from the hematopoietic system are considered multipotent?

<p>Stem cells that can give rise to a range of blood cells, including red and white blood cells. (C)</p> Signup and view all the answers

What happens to germline stem cells after they differentiate into mature germ cells?

<p>They become terminally differentiated and cannot proliferate. (A)</p> Signup and view all the answers

Which statement correctly describes the function of unipotent germline stem cells?

<p>They produce either sperm or oocytes but not both. (D)</p> Signup and view all the answers

What does the term 'totipotent zygote' refer to in the context of germ cell development?

<p>A fertilized egg that has the potential to develop into any cell type. (A)</p> Signup and view all the answers

What is the significance of somatic genes being down-regulated in germ cells?

<p>It helps maintain the distinct identity of germ cells. (A)</p> Signup and view all the answers

What role does global DNA methylation changes play during embryonic development?

<p>It erases epigenetic imprints for cell reprogramming. (D)</p> Signup and view all the answers

How do male and female epigenetic patterns differ in germ cells?

<p>Male germ cells are prepared for spermatogenesis, while female are for oogenesis. (B)</p> Signup and view all the answers

At what stage do female germ cells pause during meiosis?

<p>Prophase I (B)</p> Signup and view all the answers

When do male germ cells begin their meiotic process?

<p>At puberty (B)</p> Signup and view all the answers

What is the main difference in reproduction between male and female germ cells following puberty?

<p>Males produce sperm throughout life, while females arrest oocytes until fertilization. (A)</p> Signup and view all the answers

What is an essential factor for establishing the correct epigenetic environment in germ cells?

<p>Proper epigenetic reprogramming. (C)</p> Signup and view all the answers

How do extended meiosis stages affect female germ cells?

<p>They remain arrested at various meiosis stages until fertilized. (C)</p> Signup and view all the answers

What maintains the distinct identity of germ cells during development?

<p>Down-regulation of somatic cell functions. (C)</p> Signup and view all the answers

How do primordial germ cells (PGCs) initially differ in their development?

<p>They start as a bipotential cell type with the potential to become either sperm or eggs. (D)</p> Signup and view all the answers

What markers do primordial germ cells express during their early development?

<p>Oct4, Nagog, and Sox2 (D)</p> Signup and view all the answers

What occurs to primordial germ cells when they migrate to the gonadal ridge in the male?

<p>They enter a mitotic arrest before further differentiation. (C)</p> Signup and view all the answers

How does the activation of the SRY gene affect primordial germ cells?

<p>It promotes the differentiation of PGCs into male germ cells. (D)</p> Signup and view all the answers

Which process occurs in female gonads after primordial germ cells enter meiosis?

<p>They arrest at prophase I until fertilization. (D)</p> Signup and view all the answers

What is the role of SOX9 in male gonad development?

<p>It promotes FGF9 expression necessary for differentiation. (B)</p> Signup and view all the answers

At which stage do male primordial germ cells start spermatogenesis?

<p>At puberty. (A)</p> Signup and view all the answers

What is the function of FGF9 in the development of male germ cells?

<p>It promotes the proliferation and differentiation of male germ cells. (D)</p> Signup and view all the answers

What sequence of events characterizes the male embryonic development of primordial germ cells?

<p>SRY gene activation, differentiation into male germ cells, formation of seminiferous cords. (B)</p> Signup and view all the answers

Flashcards

Germline stem cells (GSCs)

Cells that are capable of dividing to produce both more stem cells and specialized germ cells (sperm or oocytes).

Unipotent

Unipotent refers to a stem cell that can only develop into one specific type of cell, in this case, sperm or oocytes.

Terminally differentiated

A cell that has reached its final stage of development and cannot further divide or differentiate.

Totipotent zygote

The fertilized egg cell, which has the potential to develop into any cell type of the organism.

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Germline differentiation

The process by which germline stem cells produce mature sperm or oocytes.

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Genomic quality of germ cells

The genetic material carried within sperm and oocytes, which is passed down to offspring.

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Genetic defects in germ cells

Genetic defects present within germ cells pose a risk of being inherited by offspring, potentially causing developmental abnormalities or disorders.

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Epigenetic Reprogramming

The process of removing epigenetic marks from somatic cells, allowing germ cells to revert to a blank slate for reprogramming.

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Somatic Genes Down-Regulated

The process of switching on genes that are specific to germ cells, while silencing genes that are specific to somatic cells.

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Global DNA Methylation Changes

The process of reducing levels of 5-methylcytosine in DNA, which helps remove epigenetic imprints.

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Male vs. Female Epigenetic Patterns

Germ cells inherit different epigenetic patterns depending on whether they will develop into sperm or eggs.

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Spermatogenesis

A process that begins at puberty in males and continues throughout life, resulting in the continuous production of sperm.

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Oogenesis: Arrested in Prophase I

The process of a female germ cell (oocyte) pausing its development in prophase I of meiosis during embryogenesis.

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Oogenesis: Entry into Meiosis

The process of female germ cells (oogonia) entering meiosis during embryogenesis.

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Oogenesis: Completion at Fertilization

The process of female germ cells completing meiosis only upon fertilization.

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Oogenesis

A process that begins with a group of cells called oogonia, which pause their development and await fertilization.

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Bipotential PGCs

Primordial germ cells (PGCs) are the precursors of sperm and eggs, initially capable of becoming either one.

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Pluripotent PGCs

PGCs maintain their potential to become many cell types, including sperm or eggs, even as they journey to the gonads.

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PGC Migration

The journey PGCs undertake to reach the gonads, where they'll become sperm or eggs.

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Spermatogonia in Testis

In the testis, PGCs enter a state of rest, waiting to become sperm at puberty.

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Oocytes in Ovary

In the ovary, PGCs enter meiosis but pause in the early stages, resuming and completing the process later.

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SRY Gene Activation

The Y chromosome carries a gene called SRY, which is responsible for initiating the development of male characteristics.

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SOX9 Gene Role

SOX9, a gene activated by SRY, plays a crucial role in male germ cell development and testis formation.

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FGF9 Function

FGF9 is a growth factor that promotes testis development, influenced by SOX9.

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Male Germ Cell Differentiation

A cascade of genes, starting with SRY, leads to the development of male germ cells and the formation of seminiferous cords, the building blocks of the testis.

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Seminiferous Cords Function

These cords, formed in the testis, are essential for spermatogenesis, the process of making sperm.

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SSCs Self-Renewal

Spermatogonial stem cells (SSCs) have the ability to divide and create more SSCs, ensuring a continuous supply of germ cells for spermatogenesis.

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SSCs Differentiation

SSCs can differentiate into sperm-producing cells, demonstrating their key role in spermatogenesis.

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SSCs Repopulation of Testes

The study injected LacZ+ tagged SSCs into testes lacking germ cells, demonstrating that SSCs can repopulate the testes and restore spermatogenesis.

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β-galactosidase Staining

The presence of β-galactosidase activity in the testes of recipient mice confirmed that the injected LacZ+ SSCs successfully repopulated the testes.

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SSCs Functional Spermatogenesis

The repopulated testes produced sperm, indicating the functional ability of the injected LacZ+ SSCs to contribute to normal spermatogenesis.

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Spermatozoa release and maturation

The process of mature sperm being released into the seminiferous tubules and then transported to the epididymis for further maturation.

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Final sperm maturation

The stage at which sperm acquire full motility and the ability to fertilize an egg.

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Spermatogonial stem cell renewal in embryo

Spermatogonial stem cells are primarily undergoing self-renewal to establish the future stem cell pool.

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Spermatogenesis in childhood

Spermatogonia are present and proliferate, but meiosis and spermatogenesis are not actively occurring.

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Spermatogenesis at puberty onset

Spermatogonial stem cells begin the process of differentiation, with one daughter cell maintaining the stem cell population and the other progressing through meiosis and spermiogenesis.

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Spermatogenesis in adulthood

Spermatogenesis is a continuous process, with millions of sperm being produced daily.

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Oocyte arrest in prophase I

The process of a female germ cell (oocyte) pausing its development in prophase I of meiosis during embryogenesis.

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Oogonia entry into meiosis

The process of female germ cells (oogonia) entering meiosis during embryogenesis.

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Oocyte completing meiosis

The process of female germ cells completing meiosis only upon fertilization.

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Oogenesis overview

A process that begins with a group of cells called oogonia, which pause their development and await fertilization.

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Study Notes

Germline Stem Cells (GSCs)

  • Produce gametes (sperm or oocytes)
  • Unipotent: Can only produce one type of cell (sperm or oocytes).
  • Unlike multipotent stem cells which can differentiate into multiple cell types.

Germ Cell Specification

  • Two types:
    • Determinative: Inherited factors (insects, worms, frogs, fish)
    • Regulative: Induced by signalling factors (mammals)
    • Germ plasm unevenly distributed during early embryonic development in determinative specification; molecular signals like Nanos mark cells destined to become germ cells

Mammalian Germline Induction

  • BMP (bone morphogenetic protein) from extraembryonic ectoderm, especially BMP4 and BMP8B, initiate changes that lead to germ cell formation.
  • BMP antagonists restrict BMP signaling to proximal epiblast to ensure placement.

Germ Cell Development

  • Germ cells originate from the early embryo.
  • Cells migrate to the genital ridges (ovaries or testes.)
  • They undergo meiosis at puberty, leading to sperm or oocytes

Activation of Pluripotency

  • Crucial factors: Oct4, Sox2, Nanog, and Nanos3 maintain pluripotency, allowing cells to differentiate into a variety of cells.

Germ Cell Genes

  • Oct4: Maintains pluripotency
  • Sox2: Part of pluripotency network
  • Nanog: Maintains germline's undifferentiated state
  • Nanos3: Part of pluripotency network involved in germline development

Mammalian Germ Cells

  • Not pre-determined by cytoplasmic determinants, but induced by signals from extra-embryonic tissues.

Germ Cell Differentiation

  • Markers: Blimp1, Prdm14, Sox2, Stella and Nanos3.
  • Transcription factors to maintain germline identity and establish the epigenetic landscape.

Epigenetic Reprogramming

  • Crucial for resetting epigenetic imprints for germ cells prior to fertilization.
  • Global demethylation (reduction of 5-methylcytosine) prepares germ cells.
  • Epigenetically programmed differently depending on sex (male or female).

Spermatogenesis

  • Male gamete production.
  • Stages: Spermatogonia, primary spermatocytes, secondary spermatocytes, spermatids and spermatozoa.
  • Spermatogonial stem cell (SSCs): Continuous sperm production throughout adult life.

Spermatogonial Stem Cells (SSC)

  • Primitive spermatogonia.
  • Responsible for continuous sperm production.
  • Located at the periphery of the seminiferous tubules, undergo self-renewal and differentiation.

Postnatal Development

  • Increase in Retinoic Acid levels in males during puberty to initiate the initial stage of meiosis.
  • Peak STRA8 expression in males shortly after birth marking the transition to meiosis.

Aging and SSC

  • The niche supporting SSC decline with aging, leading to a loss of germ cells.
  • Lower GDNF levels in aging males contributing to the decline in SSC function,
  • Reduced GDNF leads to impaired spermatogenesis.

Spermatogonial Stem Cell Niche

  • Crucial for SSC maintenance: Sertoli cells, FGF2, CSF1, and CXCL12 play a vital role.
  • Extrinsic factors supporting SSC survival.

Markers and Selection of SSC

  • LacZ+ staining identifies and confirms SSC repopulation and spermatogenesis.

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