M5-Lecture1

Question 1

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

Answer 1

Gametogenesis

Question 2

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

Answer 2

Spermatogenesis
Oogenesis

Question 3

Spermatogenesis produce what:
And what do Oogenesis form

Answer 3

Spermatogenesis: Spermatozoa (sperm cells)
Oogenesis: form ova (egg cells)

Question 4

Oogenesis and S. process:

Answer 4

Summary of Key Points: Oogenesis
undergoes mitosis
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).

Question 5

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.

Question 6

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.

Answer 6

True

Question 7

Where does sperm production take place:

Answer 7

Seminiferous Tubules

Separated from the systemic circulation by blood-testis barrier.

Question 8

Function of rete testis

Answer 8

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

Question 9

What forms the blood-testis barrier:

Their importance:

Answer 9

Tight junctions between Sertoli 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.

Question 10

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

Answer 10

Leydig cells

Question 11

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

Question 12

Which hormones stimulate spermatogenesis and testosterone secretion by testes:

Answer 12

LH and FSH

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

Question 13

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

Answer 13

Testosterone (from leydig cells) - both and inhibin (from sertoli cells) - anterior p.

Question 14

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

Answer 14

Spermatogonia (Spermatogonium)

Question 15

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

Answer 15

Type A Primary spermatocytes, which undergo meiosis

Question 16

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

Answer 16

True

Spermiation

Question 17

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

Answer 17

True

Question 18

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

Answer 18

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.

Question 19

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

Answer 19

Most comes from seminal fluid, prostate fluid, bulbourethral glands

Question 20

Mature sperm components:

Answer 20

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

Question 21

Primary cause of infertility:

Answer 21

Male factor (epigenetic reprogramming)

Reasons:
Low sperm conc.
poor sperm motility
abnormal morphology

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

Environment/lifestyle is impactful

Question 22

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.

Answer 22

True

Question 23

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.

Question 24

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

Answer 24

True

Question 25

Meiotic errors are very common in humans

Answer 25

True

Question 26

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

Answer 26

True

Question 27

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

Answer 27

True

Question 28

See diagram on sperm abnormalities

Question 29

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

Answer 29

True

Question 30

Chromatin organization in sperm and oocytes is markedly different

Answer 30

True

Question 31

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

Answer 31

True

Question 32

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

Answer 32

Protamines

Question 33

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

Question 34

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

Question 35

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

Answer 35

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

Question 36

Spermatogenesis produces what is essentially a motile nucleus

Answer 36

True

Question 37

produces a gamete that contains all the materials needed to initiate and maintain metabolism and development? The egg develops a remarkably complex cytoplasm

Answer 37

Oogenesis

Question 38

Oogenesis begins in the fetus before birth

Answer 38

True

Question 39

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

Answer 39

Primordial germ cells

Question 40

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

Answer 40

Primary oocytes

Question 41

During childhood, further atresia (cell death) see diagram

Answer 41

True

Question 42

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.

Answer 42

See diagram

Question 43

The primary oocytes undergo 3 stages:

Answer 43

Pre-antral Antral Preovulatory

Question 44

Pre-Antral stage:

Answer 44

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 the theca folliculi (responsive to LH, secrete androgens)

Question 45

Antral Stage:

Answer 45

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.

Question 46

Pre-Ovulatary Stage:

Answer 46

LH surge, meiosis I now is compelet. 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

Question 47

is formed by both granulosa cells and thecal cells after ovulation has occurred Hint: wall of collapsed follicle (folded-structure)

Answer 47

Corpus leutum

Question 48

Functions of CL

Answer 48

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

Question 49

See Oogenesis summary diagram

Question 50

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

Question 51

Pathology, environmental factors, aging, diet: see diagram

Answer 51

Impact oogenesis

Question 52

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

Answer 52

True

Question 53

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

Answer 53

True

Question 54

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.

Answer 54

See the diagram

Question 55

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

Answer 55

True

Question 56

Describe steps of fertilization, sperm meets ovum:

Answer 56

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

Question 57

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

Answer 57

True

Question 58

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

Answer 58

20um in diameter

Question 59

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

Answer 59

True

Question 60

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

Question 61

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

Question 62

The stages of fertilization can be divided into four processes

Answer 62

sperm preparation, sperm-egg recognition and binding, sperm-egg fusion cortical reaction fusion of sperm and egg pronuclei and activation of the zygote

Question 63

Sperm preparation:

Answer 63

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

Question 64

Fertilization can occur after removing inhibitory factors, such as

Answer 64

surface-attached glycoproteins, seminal plasma proteins and depletion of membrane cholesterol

Question 65

Sperm-egg recognition and binding

Answer 65

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

Question 66

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

Answer 66

True

Question 67

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

Answer 67

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

Question 68

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

Answer 68

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

Question 69

Prevention of entry of other sperm is achieved by two mechanisms

Answer 69

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: the cortical 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 a fertilization 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.

Question 70

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.

Question 71

Fusion of Pronuclei:

Answer 71

After sperm and egg membranes fuse, the sperm's nucleus forms the male pronucleus, while the egg completes meiosis and forms the female pronucleus. Both pronuclei enlarge, migrate toward each other, and replicate DNA. Upon meeting, their nuclear envelopes break down, chromosomes condense, and a mitotic spindle forms, marking the formation of the zygote at the 2-cell stage.