M5-Lecture1 Flashcards
Gametogenesis, Fertilization and Critical Windows
Process whereby a haploid cell (n) is formed from a diploid cell (2n) through meiosis and cell differentiation
Gametogenesis
Gametogenesis in male is known as and in female is known as
Spermatogenesis
Oogenesis
Spermatogenesis produce what:
And what do Oogenesis form
Spermatogenesis: Spermatozoa (sperm cells)
Oogenesis: form ova (egg cells)
Oogenesis and S. process:
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).
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.
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.
True
Where does sperm production take place:
Seminiferous Tubules
Separated from the systemic circulation by blood-testis barrier.
Function of rete testis
Collects sperm from the ST and transports it into the epididymis where they mature until ejaculation.
What forms the blood-testis barrier:
Their importance:
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.
What are mixed in the wall of tubules and produce high level of testosterone once male reaches adolescence.
Leydig cells
After sperm are released into the lumen of the seminiferous tubules, they move through the tubuli recti (straight tubules) to the rete testis.
Which hormones stimulate spermatogenesis and testosterone secretion by testes:
LH and FSH
Hypo. - GnRH - anterior pituitary stimulate - Lh and FSH (sertoli and leydig cells)
These two inhibit secretion of GnRH by the hypo. and LH and FSH by the pituitary.
Testosterone (from leydig cells) - both and inhibin (from sertoli cells) - anterior p.
Are initial pool of diploid cells that divide by mitosis to give two identical cells:
Spermatogonia (Spermatogonium)
Type B spermatogonia replicate by mitosis many times to form identical diploid cells linked by cytoplasmic bridges to produce
Type A Primary spermatocytes, which undergo meiosis
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
True
Spermiation
Spermatogenesis take roughly 70 days, but to keep producing sperms, every 16 days simultaneous spermatogenic process must occur
True
In the female reproductive tract, the conditions there cause the sperm to undergocapacitation
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.
Spermatozoa need the nutrient-rich fluids produced by accessory glands to survive, move, and fertilize an egg.
Most comes from seminal fluid, prostate fluid, bulbourethral glands
Mature sperm components:
head (contains nucleus, acrosome), neck, middle piece (mitochondrion - spiral shape), plasma membrane, tail.
Primary cause of infertility:
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
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.
True
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.
Research shows structural anomalies (i.e., chromosome breaks) more common than numerical abnormalities.
True
Meiotic errors are very common in humans
True
All chromosomes are susceptible to non-disjunction, especially chromosomes 21 and 22 and sex chromosomes
True
Significant increase of structural abnormalities with paternal age, but no evidence of aneuploidy.
True
See diagram on sperm abnormalities
Understanding sperm epigenetics will be beneficial for human assisted reproductive therapy (ART)
True
Chromatin organization in sperm and oocytes is markedly different
True
Sperm DNA tightly packed, histones replaced with protamines,
a lot of DNA methylation - compared to oocytes & more open chromatin
True
are basic proteins that wrap around DNA more stringently than histones and create compact structures to protect the DNA
Protamines
Protamines can also undergo post-translational modification such as phosphorylation, the purpose of which is poorly understood
See diagram
Epigenetic modification occurs throughout spermatogenesis (such as histone tail modifications & transcription of RNA molecules
See diagram
These periods of programming occur during crucial developmental time points (windows of susceptibility for epigenetic errors) which can impact fertility & embryonic competence:
Chromatin remodeling
Epigenetic modification level
Ex:
- Paternal DNA methylation
- maternal DNA methylation
- H3K4/9/27 methylation
Spermatogenesis produces what is essentially a motile nucleus
True
produces a gamete that contains all the materials needed to initiate and maintain metabolism and development?
The egg develops a remarkably complex cytoplasm
Oogenesis
Oogenesis begins in the fetus before birth
True
move to colonize the cortex of the primordial gonad and replicate by mitosis to peak at approximately 7 million by mid-gestation (~20 weeks).
Primordial germ cells
Cell death occurs after this peak to leave 2 million cells which begin meiosis I before birth, these are known as
Primary oocytes
During childhood, furtheratresia(cell death)
see diagram
True
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.
See diagram
The primary oocytes undergo 3 stages:
Pre-antral
Antral
Preovulatory
Pre-Antral stage:
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)
Antral Stage:
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.
Pre-Ovulatary Stage:
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
is formed by both granulosa cells and thecal cells after ovulation has occurred
Hint: wall of collapsed follicle (folded-structure)
Corpus leutum
Functions of CL
Endocrine organ (progesterone and estrogen) - supporting pregnancy & preventing menstruation
See Oogenesis summary diagram
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
Pathology, environmental factors, aging, diet: see diagram
Impact oogenesis
The profile of DNA methylation remains constant at the primordial stage to the stage of primary follicles, but it increases progressively until antrum formation.
True
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
True
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.
See the diagram
The changed nutrition supplies, especial one-carbon, may contribute to epigenetic changes in aged oocytes
True
Describe steps of fertilization, sperm meets ovum:
- Sperm makes contact with egg.
- Acrosome with zona pellucida
- Acrosome reacts with perivitelline space
- Plasma membrane of sperm and egg fuse
- Sperm nucleus enters egg
- Cortical granules fuse with egg PM, renders viteline layer impenetrable to sperm
The sperm can survive for 3–5 days inside the vagina
True
Oocytes acquire the ability to fuse with sperm when they reach blank in size
20um in diameter
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.
True
The secondary oocyte will only complete meiosis II followingfertilization,giving off a third polar body once meiosis II is completed and a fertilized egg
If fertilization never occurs, the oocyte degenerates 24 hours after ovulation, remaining arrested in meiosis II
The stages of fertilization can be divided into four processes
sperm preparation,
sperm-egg recognitionand binding,
sperm-egg fusioncortical reaction
fusion of sperm and egg pronuclei and activation of the zygote
Sperm preparation:
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
Fertilization can occur after removing inhibitory factors, such as
surface-attached glycoproteins,
seminal plasma proteins
and
depletion of membrane cholesterol
Sperm-egg recognitionand binding
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
As a result of irreversible binding of the sperm to the egg, the zona pellucida triggers the acrosome reaction
True
Several molecules have been identified in sperm and oocytes, with a crucial role in gamete binding
Fertilin α, fertilin β and cyritestin are also known as ADAM1, ADAM2 and ADAM3, respectively
found on the egg surface are thought to be receptors for sperm ADAMs.
Integrins
α6β1 or (α9β1) integrin is an egg receptor for fertilin β
Prevention of entry of other sperm is achieved by two mechanisms
- Fast block: near instantaneous change in sodium ion permeability. Depolarize oocyte PM to prevent other sperms from binding. Lasts a minute, influx of Ca2+
- 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.
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.
Fusion of Pronuclei:
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.
