M5-Lecture1 Flashcards

Gametogenesis, Fertilization and Critical Windows

1
Q

Process whereby a haploid cell (n) is formed from a diploid cell (2n) through meiosis and cell differentiation

A

Gametogenesis

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2
Q

Gametogenesis in male is known as and in female is known as

A

Spermatogenesis
Oogenesis

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3
Q

Spermatogenesis produce what:
And what do Oogenesis form

A

Spermatogenesis: Spermatozoa
Oogenesis: form ova

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4
Q

Oogenesis and S. process:

A

Summary of Key Points: Oogenesis
Primary oocyte (2n) → undergoes meiosis I → secondary oocyte 1(n) + polar body 1(n).
Secondary oocyte undergoes meiosis II only if fertilized:
If fertilized: forms haploid ovum 1(n) + 1(n) sperm becomes 2n(zygote) + polar body 1(n).
If not fertilized: the secondary oocyte degenerates.

S.Summary of Key Stages:
Spermatogonia (2n) → undergo mitosis → more spermatogonia.
Some spermatogonia differentiate into primary spermatocytes (2n).
Primary spermatocyte (2n) undergoes meiosis I → secondary spermatocytes two (n).
Secondary spermatocytes (n) undergo meiosis II → spermatids four (n).
Spermatids (n) undergo spermiogenesis → spermatozoa (n) (mature sperm).

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5
Q

Key Differences Between Oogenesis and Spermatogenesis in Terms of Mitosis:

Oogenesis:
Mitosis occurs only during fetal development to produce oogonia.
After birth, no more mitosis occurs in the ovaries. The number of primary oocytes remains fixed.

Primary oocytes undergo meiosis I, but only one oocyte typically completes meiosis to become a mature ovum.

Spermatogenesis:
Mitosis occurs throughout life to continually produce spermatogonia, the stem cells that give rise to sperm.

Spermatogonia undergo mitosis to maintain a supply of stem cells and generate more primary spermatocytes.

Primary spermatocytes undergo meiosis to form secondary spermatocytes, and eventually four sperm cells per primary spermatocyte.

A
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6
Q

Males start producing sperm when they reach puberty (10-16 years old)

Produced in large quantities (2 million a day)

efficient at 34 degree C.

A

True

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7
Q

Where does sperm production take place:

A

Seminiferous Tubules

Separated from the systemic circulation by blood-testis barrier.

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8
Q

Function of rete testis

A

Collects sperm from the ST and transports it into the epididymis where they mature until ejaculation.

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9
Q

What forms the blood-testis barrier:

Their importance:

A

Tight junctions between Steroli cells (“nurse” cell) in the ST, help in the process of spermatogenesis)

Produce fluid and control release of sperm into the lumen

Secrete inhibin to slow s. production

Prevent hormones and constituents of systemic circulation from affecting developing sperm.

Prevents immune system from recognizing the sperm as foreign.

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10
Q

What are mixed in the wall of tubules and produce high level of testosterone once male reaches adolescence.

A

Leydig cells

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11
Q

After sperm are released into the lumen of the seminiferous tubules, they move through the tubuli recti (straight tubules) to the rete testis.

A
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12
Q

Which hormones stimulate spermatogenesis and testosterone secretion by testes:

A

LH and FSH

Hypo. - GnRH - anterior pituitary stimulate - Lh and FSH (sertoli and leydig cells)

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13
Q

These two inhibit secretion of GnRH by the hypo. and LH and FSH by the pituitary.

A

Testosterone (from leydig cells) and inhibin (from sertoli cells)

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14
Q

Are initial pool of diploid cells that divide by mitosis to give two identical cells:

A

Spermatogonia (Spermatogonium)

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15
Q

Type B spermatogonia replicate by mitosis many times to form identical diploid cells linked by cytoplasmic bridges to produce

A

Type A Primary spermatocytes, which undergo meiosis

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16
Q

However, one of the diploid cells will replenish the pool of spermatogonia

While type B will form mature sperm, once spermatid mature and differentiate (cytoplasmic bridge breaks and spermatids are released into the lumen of ST a process called

A

True

Spermiation

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17
Q

Spermatogenesis take roughly 70 days, but to keep producing sperms, every 16 days simultaneous spermatogenic process must occura

A

True

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18
Q

In the female reproductive tract, the conditions there cause the sperm to undergocapacitation

A

removal of cholesterol and glycoproteins from the head (which it got from epididymal) of the sperm cell to bind to the zona pellucida of the egg cell.

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19
Q

Spermatozoa need the nutrient-rich fluids produced by accessory glands to survive, move, and fertilize an egg.

A

Most comes from seminal fluid, prostate fluid, bulbourethral glands

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20
Q

Mature sperm components:

A

head (contains nucleus, acrosome), neck, middle piece (mitochondrion - spiral shape), plasma membrane, tail.

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21
Q

Primary cause of infertility:

A

Male factor (epigenetic reprogramming)

Reasons:
Low sperm conc.
poor sperm motility
abnormal morpholgy

Higher in less industrialized countries, as well as risk of infection

Environment/lifestyle is imapctful

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22
Q

While Sertoli cells support sperm in the seminiferous tubules of the testes, once the sperm move into the epididymis, they are nourished by the epididymal fluid produced by epididymal epithelial cells.

A

True

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23
Q

While sperm cells (spermatids and spermatozoa) receive nourishment and support from Sertoli cells within the seminiferous tubules, the additional seminal fluid that provides energy and helps with sperm motility is introduced later in the vas deferens and urethra.

A
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24
Q

Research shows structural anomalies (i.e., chromosome breaks) more common than numerical abnormalities.

A

True

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25
Q

Meiotic errors are very common in humans

A

True

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26
Q

All chromosomes are susceptible to non-disjunction, especially chromosomes 21 and 22 and sex chromosomes

A

True

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27
Q

Significant increase of structural abnormalities with paternal age, but no evidence of aneuploidy.

A

True

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28
Q

See diagram on chromosome abnormalities

A
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29
Q

Understanding sperm epigenetics will be beneficial for human assisted reproductive therapy (ART)

A

True

30
Q

Chromatin organization in sperm and oocytes is markedly different

A

True

31
Q

Sperm DNA tightly packed, histones replaced with protamines,
a lot of DNA methylation - compared to oocytes & more open chromatin

A

True

32
Q

are basic proteins that wrap around DNA more stringently than histones and create compact structures to protect the DNA

A

Protamines

33
Q

Protamines can also undergo post-translational modification such as phosphorylation, the purpose of which is poorly understood

See diagram

A
34
Q

Epigenetic modification occurs throughout spermatogenesis (such as histone tail modifications & transcription of RNA molecules

See diagram

A
35
Q

These periods of programming occur during crucial developmental time points (windows of susceptibility for epigenetic errors) which can impact fertility & embryonic competence:

A

Chromatin remodeling

Epigenetic modification level
Ex:
- Paternal DNA methylation
- maternal DNA methylation
- H3K4/9/27 methylation

36
Q

Spermatogenesis produces what is essentially a motile nucleus

A

True

37
Q

produces a gamete that contains all the materials needed to initiate and maintain metabolism and development?

The egg develops a remarkably complex cytoplasm

A

Oogenesis

38
Q

Oogenesis begins in the fetus before birth

A

True

39
Q

move to colonize the cortex of the primordial gonad and replicate by mitosis to peak at approximately 7 million by mid-gestation (~20 weeks).

A

Primordial germ cells

40
Q

Cell death occurs after this peak to leave 2 million cells which begin meiosis I before birth, these are known as

A

Primary oocytes

41
Q

During childhood, furtheratresia(cell death)

see diagram

A

True

42
Q

Three polar bodies are typically produced by the time oogenesis is complete:
1 polar body from Meiosis I.
1 polar body from Meiosis II (if fertilized).
A third polar body could form if the first polar body undergoes a second division, which happens rarely but is possible.

A

See diagram

43
Q

The primary oocytes undergo 3 stages:

A

Pre-antral
Antral
Preovulatory

44
Q

Pre-Antral stage:

A

The primary oocyte grows dramatically whilst still being arrested in meiosis I.

The follicular cells grow and proliferate to form cuboidal epithelium. These cells, granulosa cells, secrete glycoproteins to form zona pellucida around primary oocyte:

Surrounding connective tissue cells also differentiates to become thetheca folliculi (responsive to LH, secrete androgens)

45
Q

Antral Stage:

A

Fluid filled spaces form between granulosa cells, eventually form antrum.

Follicles are now secondary follicles

In each monthly cycle one of these secondary follicles becomes dominant and develops further under the influence of FSH, LH and estrogen.

46
Q

Pre-Ovulatary Stage:

A

LH surge, meiosis I now is compelte.

Two haploid cells are formed within the follicle; one daughter cell and one polar body,

The other haploid cell is called secondary oocyte

Both daughter cells undergo meiosis II The first polar body will replicate to give two polar bodies but the secondary oocyte arrests in metaphase of meiosis II, 3 hours prior to ovulation

Ovulation:
Follicle is larger, called Graafian follicle

The LH surge increases collagenase activity so that the follicular wall is weakened, this combined with muscular contractions of the ovarian wall result in the ovum being released from the ovary

47
Q

is formed by both granulosa cells and thecal cells after ovulation has occurred

Hint: wall of collapsed follicle (folded-structure)

A

Corpus leutum

48
Q

Functions of CL

A

Endocrine organ (progesterone and estrogen) - supporting pregnancy & preventing menstruation

49
Q

See Oogenesis summary diagram

A
50
Q

Many Oogenesis have numerical abnormalities, either in first M1 (most) or MII.

All chromosomes are susceptible to error during oogenesis, especially small chromosomes

Maternal age has long been recognized as the most significant factor in the etiology of aneuploidy

A
51
Q

Pathology, environmental factors, aging, diet: see diagram

A

Impact oogenesis

52
Q

The profile of DNA methylation remains constant at the primordial stage to the stage of primary follicles, but it increases progressively until antrum formation.

A

True

53
Q

During the early stages of development, histone acetylation has a low level and begins to rise abruptly along with the follicle development of oocytes (which can be impacted by epigenetic modification by maternal age.

20% vs 50% of aneuploidy discripancy btw. young and old mothers

Histone methylation also exists

A

True

54
Q

External: assisted reproductive technology procedures (ART), parental diets, and unhealthy parental habits, may disturb the epigenetic reprogramming processes and lead to an aberrant epigenome in the offspring.

A

See the diagram

55
Q

The changed nutrition supplies, especial one-carbon, may contribute to epigenetic changes in aged oocytes

A

True

56
Q

Describe steps of fertilization, sperm meets ovum:

A
  1. Sperm makes contact with egg.
  2. Acrosome with zona pellucida
  3. Acrosome reacts with perivitelline space
  4. Plasma membrane of sperm and egg fuse
  5. Sperm nucleus enters egg
  6. Cortical granules fuse with egg PM, renders viteline layer impenetrable to sperm
57
Q

The sperm can survive for 3–5 days inside the vagina

A

True

58
Q

Oocytes acquire the ability to fuse with sperm when they reach blank in size

A

20um in diameter

59
Q

The acrosome contains proteolytic enzymes, such as acrosin, trypsin, hyaluronidase and proteases, which are released during the acrosome reaction and they are arrested at the prophase of meiosis II.

A

True

60
Q

The secondary oocyte will only complete meiosis II followingfertilization,giving off a third polar body once meiosis II is completed and a fertilized egg

A
61
Q

If fertilization never occurs, the oocyte degenerates 24 hours after ovulation, remaining arrested in meiosis II

A
62
Q

The stages of fertilization can be divided into four processes

A

sperm preparation,

sperm-egg recognitionand binding,

sperm-egg fusioncortical reaction

fusion of sperm and egg pronuclei and activation of the zygote

63
Q

Sperm preparation:

A

It occurs in the genital tract of the female, and acts as a preparatory step for the acrosome reaction

Intracellular Ca++ levels increase

hyperactivation (flagellar movement & swimming capacity)

Glucose necessary for capacitation (energy for swimming) and enable fertilization

Progesterone also needed for capacitation, hyper activated motility, acrosome reaction, sperm-ZP binding and sperm oocyte fusion

64
Q

Fertilization can occur after removing inhibitory factors, such as

A

surface-attached glycoproteins,

seminal plasma proteins

and
depletion of membrane cholesterol

65
Q

Sperm-egg recognitionand binding

A

To reach the oocyte itself, the sperm must penetrate the two protective layers (Corona radiata and ZP) - after binding to ZP - triggers acrosomal rxn causing sperm to secrete digestive enzymes that breakdown the glycoprotein membrane of zona pellucida and allow sperm to reach oocyte.

The sperm reaching the transparent zone is connected via SED1 protein to ZP3

The membrane fusion process can be divided into three key events:

First attachment: protein-protein or p-carbohydrate mediated binding

Second membrane apposition: two membranes come closer, hinge like motion brings membrane inserted proteins closer, pulling the membrane as well.

Third, lipid mixing: once membranes close, lipid mixing occurs, leading to cytoplasmic continuity btw. two cells

66
Q

As a result of irreversible binding of the sperm to the egg, the zona pellucida triggers the acrosome reaction

A

True

67
Q

Several molecules have been identified in sperm and oocytes, with a crucial role in gamete binding

A

Fertilin α, fertilin β and cyritestin are also known as ADAM1, ADAM2 and ADAM3, respectively

68
Q

found on the egg surface are thought to be receptors for sperm ADAMs.

A

Integrins

α6β1 or (α9β1) integrin is an egg receptor for fertilin β

69
Q

Prevention of entry of other sperm is achieved by two mechanisms

A
  1. Fast block: near instantaneous change in sodium ion permeability. Depolarize oocyte PM to prevent other sperms from binding. Lasts a minute, influx of Ca2+
  2. Slow block: after penetration.

After:
thecortical reaction, cortical granules sitting immediately below the oocyte plasma membrane fuse with the membrane and release zonal inhibiting proteins and mucopolysaccharides into the space between the plasma membrane and the zona pellucida. Zonal inhibiting proteins cause release of any other attached sperm and destroy oocytes sperm receptors

The mucopolysaccharides then coat the nascent zygote in an impenetrable barrier that, together with hardened zona pellucida, is called afertilization membrane.

At the point of fertilization, the oocyte has not yet completed meiosis; all secondary oocytes remain arrested in metaphase of meiosis II until fertilization

The unneeded complement of genetic material that results is stored in a second polar body that is eventually ejected.

At this moment, the oocyte has become an ovum, the female haploid gamete.

70
Q

The two haploid nuclei derived from the sperm and oocyte and contained within the egg are referred to as pronuclei. They decondense, expand, and replicate their DNA in preparation for mitosis.

A
71
Q

Fusion of Pronuclei:

A

Fusion of Pronuclei:

Sperm and Egg Interaction: After sperm and egg plasma membranes fuse, the sperm nucleus and its centriole separate from the mitochondria and flagellum, which disintegrate in the egg.

Male Pronucleus Formation: The sperm nucleus decondenses to form the male pronucleus. The nuclear envelope breaks down, exposing the sperm chromatin to the egg cytoplasm.

Chromatin Decondensation: Protamines in the sperm chromatin are replaced by egg-derived proteins, allowing the chromatin to decondense.

Enlargement of Pronuclei:

The male pronucleus enlarges while the oocyte completes its second meiotic division. The centrosome from the male pronucleus forms asters and contacts the female pronucleus.

Pronuclear Migration:

Both pronuclei migrate toward each other, replicating DNA during migration.

Fusion and Zygote

Formation: Upon meeting, the nuclear envelopes break down, the chromatin condenses into chromosomes, and a common mitotic spindle forms. The true diploid nucleus is first observed at the 2-cell stage, not the zygote stage.

72
Q
A