module 2: Gametogenesis + hormonal regulation Flashcards
what allow for sexual reproduction
gametes, sperm, ova (specialized sex cells)
how are male and female gametes formed
gametogenesis
what genetic features makes gametes different from other sex cells
gametes are haploid meaning they carry half a set of chromosomes
why are gametes haploid
they half set of chromsomes so when they fuse they produce a normal diploid zygote
- theyre haploid because they divide by meiosis instead of mitosis
what is gametogenesis
is the process by which gametes are produced in sexually reproducing organism
what does the process of gametogenesis ensure:
- that gametes produced are haploid
- that gamete acquire the specialized characteristics that will allow them to fuse successfully via fertilization
how is fuse of gametes achieved
through a maturation process that ensure gametes are capable of and ready for fertilization
what do specilized germ cells undergo
meiosis to produce 4 daughter cells with only set of genetic information, or 23 unpaired chromosomes
how many divisions are in meiosis
2
- meiosis I
- meiosis II
what is meiosis I
- replicated chromosome sort themselves into homologous pair before separating, so each daughter cell receives a half set of doubled chromosome
what does meiosis I result in
2 daughter cells with half set of doubled chromosomes
what is meiosis II
the doubled chromosome within each of the 2 daughter cells separate and are distributed to 2 cells
what is the result of meiosis II
is 4 daughter cells, each containing a half set of chromosome, a single member of each pair, including the sex chromosome pair
how many phases are in gametogenesis
3
1: mitotic division
- precursor cells divide by mitotic divison
- allows for some of the cells to remain as germ cells to maintain a constant supply of new germ cells, while other half undergo maturation and become fully formed gametes
2: meiotic division
the cells destined to become gametes undergo meiotic division and divide into haploid daughter cells
3: maturation
the haploid daughter cells must undergo a process of maturation to become mature gametes
meiotic error
main cause of aneuploidy (error number of chromosomes)
- errors can occur at different points of the cell division process and can originate from either parent cell
aneuploidies of sex chromosomes
are more common that autosomal abnormalities because they are less likely to be lethal (genetic cause of many disorders of sex development)
aneuploidy
the presence of an abnormal number of chromosomes in a cell (cell having 45 or 47 chromosomes instead of the usual 46)
autosomal
pertaining to a chromosome that is not sex chromosome
where in the testes are sperm produced
the seminiferous tubules
what is permatogenesis
sperm production
what can spermatogenesis be separated into to?
- mitotic division
- meiosis I
- meiosis II
- maturation
step 1: mitotic proliferation
- primordial germ cells (spermatogonia) undergo mitotic divison to maintain a constnat supply of germ cells
each spermatogium undergoes mitotic division will?
give rise to 2 daughter cells
type A and type B spermatogonia
type A spermatogonia
will continue to replenish the spermatogonia pool
Type B spermatogonia
will divide by mitosis to produce identical primary spermatocytes which enter a resting phase in preparation for meiosis I
step 2 : meiosis I
primary spermatocytes will undergo meiosis I to produce haploid secondary spermatocytes
- each with 23 double stranded chromosomes
step 3: meiosis II
- secondary spermatocytes will undergo meiosis II to produce identical haploid cells called spermatids
what happens to secondary spermatocyte in meiosis II
divides into 2 spermatids each with 23 single stranded chromosomes
- NO further division
step 4: maturation
process of maturation is called spermiogenesis
- spermatids will lost organelles and their cytosol, nucleus will be tightly packaged
what are the mature sperm called
spermatozoa
are maturation of sperm found at specific location within the epithelium of the tubules
yes
where are spermatogonia located in maturation step
- closest to the basal membrane of the seminiferous tubules
- outermost layer of the seminiferous tubule
where do the daughter cells move too in maturation
move toward the surface of the epithelium to reach the lumen of the tubule
once mature, the spermatozoa are released how?
by the sertoli cells into the lumen of the tubule to be transported out of the testes toward the epididymis for maturation and storage
the cycle of the seminiferous epithelium
- in the spermatogenesis occurs in a wave-like pattern, refferd to as spermatogensis waves
how to do waves move
in spirals towards the inner part of the lumen
outside on the edge of the tubule and at the beginning of the spiral lie..
the spermatogonia
at the end of the spiral
- fully developed spermtozoa are in the lumen
- as cells mature they move along the tubule to give way to the new cells
how long does the process of sperm formation and maturation from newly formed tybe B spermatogonia take
64-70days
in order for sperm production to be continuous what must occur
multiple spermatogenic processes are occurring simultaneously with the same seminiferous tubule
how many cell types are required for the structure of the seminfierous tubules and completion of spermatogenesis
2
the 2 type of cells required for seminfieours tubules
leydig cells
sertoli cells
where are leydig cells located
- in the intratubular regions of the testis
- adjacent to the blood vessels
what are leydig cells responsible for
testorerone production
- essential for the maintenance of spermatogenesis
immature leydig cells
remain in a quiescent state until puberty, when they become activated under the influence of hormones released by the brain
what are sertoli cells
large, columnar cells that provide structural and nutritional support to the developing sperm cells
sertoli cells are the ________ of the testes due their vital role as supportive cells
sustentacular cells
sustentacular cells
a cell primarily associated with structural and functional support
where are sertoli cells
surround and hold onto the developing sperm cells until they mature, after which they are subsequently released
what do sertoli cells secrete
factors that are required for leydig cell development
sertoli cells
- form the blood-testis barrier by forming tight junctions with adjacent sertoli cells though their basal cytoplasmic processes
blood testis barrier
regulates the passage of substances from the circulation into the lumen of the seminiferous tubules
barrier below the blood-testis barrier
basal compartment
area above the blood testis barrier
apcial compartment
how does the blood-testis barrier protect sperm cells
- spermatogonia reside near the basement membrane of the seminiferous tubules, in the basal compartment, thus free access to factors from the interstitium
where do undergoing meiosis and maturation develop
above the blood testis barrier and thus are entirely reliant on the microenvironment created by the sertoli cells
what are blood-testis barrier, the seminferous tubules considered
an immune-privileged environment
meiotic and post-meiotic cells develop after the body has established immune tolerance
- could be recognized as “foreign” by the immune system
why do seminiferous tubules exclude immune cells
because cells could be recognized as foreign
structure of a mature sperm cell
3 main sections:
- head
- midpiece
- tail
structure of a mature sperm cell: acrosome
- top of the nucleus
- derived from the golgi apparatus
- ## contains hydrolytic enzymes that sperm will use to enter the egg
acrosome reactions
the sperm releases the contents of the acrosome to help break down the eggs protective coat to allow the sperm to reach and fertilize the egg
structure of a mature sperm cell: head
- contains DNA and hydrolytic enzymes that allow the sperm to penetrate and enter the egg for fert
- DNA in nucleus
- during maturation nucleus becomes condensed and compacted up to 6x more than normal cells to fit in the head
- cytoplasm of the spermatids is phagocytosed by the sertoli cells, along with ribosomes, E.R, and golgi leaving only a thin layer of cytoplasm around the nucleus
structure of a mature sperm cell: midpiece
contains all of the mitochondria, which create the energy used by the tail
- during maturation the mitochondria migrate towards the tail and spiral around the central filament that connect to the tail
structure of a mature sperm cell: tail
- typical flagellum composed of inner fibers that provide the scaffolding for motor proteins to bind and function
- provides the sperm with motility
structure of a mature sperm cell: end piece
the end is the last portion of the sperm tail
why is the structure of sperm important
- parameter in fertility testing as it can indicate the quality of spermatogenesis and subsequent fertility
abnormal sperm morphology
can result from a variety of disorders such as cryptorchidism, varicoceles, and genetic disorder
cryptorchidism
condition which one or both of the testes fail to descend from the abdomen into the scrotum
varicoceles
an enlargement of the veins within the scrotum
teratozoospermia
sperm with abnormal morphology
what can sperm defects prevent
motility or adherence of the sperm to the egg and affect fertility
what is oogenesis
- process where the ova are produced
oogenesis: mitotic divison
- oogonia proliferate via mitosis to produce a pool of identical daughter cells (primary oocytes)
primary oocytes
will undergo apoptosis before birth, leaving appox 2 million primary oocytes
before birth primary oocytes
initiate meiosis I but become arrested in prophase I
- remaining dormant until puberty
oogensis: meiosis I
- arrested primary oocytes will resume maturation at puberty (under influence of hormones)
- each month, before ovulation, dormant primary oocyte will complete meiosis I to produce a haploid secondary oocyte
oogensis: meiosis I - divide unevenly
- most cytoplasm of the dividing oocyte is segregated into only one of the daughter cells
- larger cell goes down the path of maturation to become an ovum
- other cell becomes a polar body
polar body
a small haploid cell that bunds off from an oocyte after meiotic divisions and does not develop into ova
oogenesis: meiosis II
- final step and completed outside the ovary
- after the secondary oocyte is released by ovulaition it will be arrested in metaphase II untill the moment of fertilization
when will oocyte undergo meiosis II
- just as the sperm fuses with the secondary oocytes to produce on ootid
ootid
turn into a mature ovum which is quickly followed by the fusion of the nuclei of sperm and ovum to form a zygote
proper formation of polar bodies
oocytes with a polar body that has improperly formed are less likely to fertilize than oocytes with normal polar bodies
the structure of the ovum
- corona radiate
- zona pellucida
- vitelline membrane
- ooplasm
- germinal vesicle
- germinal spot
corona radiate
a layer of cells surrounding the oocyte that will be released with the oocyte at ovulation; it provides vital proteins to the cell
zona pellucida
- hard shell-like structure surrounding the outside of the cell membrane; it is known to bind to the head of spermatozoa and help initiate the acrosome reaction that facilitates fertilization
vitelline membrane
the outer portion of the cell membrane
ooplasm
- also commonly called “yolk” of the egg cell, it contains the mitochondria, which will help regulate embryonic metabolism and additional factors that will aid embryonic development
germinal vesicle
this is the nucleus of the cell and contains all the genetic material of the oocyte
germinal spot
this is the nucleolus of the ovum, contained within the germinal vesicle
what are the timings of oogenesis
- fetal period
- childhood
- adulthood
fetal period
- oogonia proliferate and mature into primary oocytes peaking in number around the 20th week of fetal development
- the primary oocyte undergo apoptosis before birth leaving approx. 2 million oocytes
- cells begin meiosis I before birth and are then arrested at prophase I
where do the approx. 2 million oocytes begin meiosis I
- before birth and then arrested at prophase I
in males when does spermatogonia remain arrested
at the mitotic step
timing of oogenesis: childhood
- by time of birth, arrested primary oocytes have been surrounded by somatic cells becoming follicles in the ovary
- lots will remain dormant till puberty and some will undergo death, leaving approx 40,000 potential ova by puberty
when will primary oocytes surrounded by somatic cells remain dormant
until puberty
timing of oogenesis: adulthood
- at puberty, under the influence of hormones, gametogenesis begins
somatic cells
any cell of a living organism other than cells involved in reproduction
male adulthood
- spermatogonia begin meiotic divison and continue to proliferate to maintain the process
females adulthood
- oogenesis began before birth, so the arrested primary oocytes resume maturation following a monthly cycle
- each month a single oocyte will complete the remaining steps of oogenesis and will be released from the ovary as secondary oocyte to allow fertilization
when does permatogeneis begin for males
- at puberty
- continual process
when does oogenesis begin for females
before birth, during fetal development
- and has different steps
what is the ovarian cycle
- controlled monthly release of oocytes is vital for prolonged fertility
- females are born with finite supply of arrested oocytes when then released in a controlled fashion until the ovarian reserve is depleted
aging related hormonal changes: ovarian cycle
- results in in the eventual cessation of oogensis, onset of menopause
- even though there is germ cells present the change in reproductive function with menopause is natural process of female aging
menopause
the cessation of the reproductive cycle in women
where does oogenesis take place
mainly inside the ovaries, except the final step
what is the final step of oogenesis and where does it take place
oviduct at the moment of fertilization
where do oocytes mature
within the ovarian follicles, which are the functional unit of the ovary
what are the functions of the ovarian follicles
- they produce sex hormones that promote oogenesis and regulate pregnancy when fertilization is successful
- will grow and aid the maturation of oocytes in response to hormonal signals from the brain
what are the 2 cells in the ovarian follicles
theca cells
granulosa cells
theca cells location
surrounding the follicle
granulosa cells location
inside the follicle, surrounding the oocyte
theca cells function
produce the precursors required by granulose cells to produce estrogen and progesterone
granulosa cells function
- produce estrogen and progesterone
- numbers increase as the follicle grows and the oocyte matures
how many phases are in the ovarian cycle
2
- follicular phase
- luteal phase
what is the follicular phase
- occurs within the ovarian follicles
- follicles mature concomitantly with their oocyte in the process known as follicuogenesis
how does the follicular phase end
with ovulation (when 1 secondary oocyte is released from the ovary into the fallopian tube)
what happens during the follicular phase
- the maturing primary oocytes will complete meiosis I, becoming secondary oocytes
what is the luteal phase
- after the follicular phase
- physiological changes after ovulation to the now empty follicle
luteal phase: after ovulation
- follicle briefly becomes the corpus hemorrhagicum and later the corpus luteum
what is the corpus luteum
a structure that continues to produce the hormone progresterone to prepare the body for pregnancy
luteal phase: if no ferilization occurs
- corpus luteum will degenerate, becoming corpus albicans (mass of scar tissue) and be reaborbed and the cycle will begin again
luteal phase: if fert occurs
the corpus luteum will continue to secrete progesterone to help in the initial stages of pregnancy
the number and presence of granulosa and theca cells in follicles
changes as the follicle goes through its 4 main stages of development and maturation
phase 1: folliculogensis
primordial follicle
primordial follicle
are the dormant follicles with which females are born
they contain a primary oocyte surrounded by a single layer of flattened granulosa cells
phase 2: folliculogenesis
primary follicle
primary follicle
- after a primordial follicle becomes activated, it transitions into a primary follicle
- the granulosa cells become cuboidal, and the oocyte secretes a rigid capsule around it called the zona pellucida, separating it from the surrounding granulosa cells
phase 3: folliculogenesis
secondary follicle
secondary follicle
- forms as granulosa cells multiply, creating additional layers and theca cells are recruited to surround the outermost layer of the follicle
- some fluid begins to fill the follicle and create a cavity, known as the antrum
phase 4: folliculogenesis
tertiary follicle (graafian follicle)
tertiary follicle (graafian follicle)
- both granulosa and theca cells continue to multiply and the follicle further grows in diameter
- fluid cavity grows, forming an antrum
- eventually hormonal stimululs will cause the follicle to rupture and release the oocyte (ovulation) along with a thick layer of granulosa cells
the released oocyte
will complete the final meiotic division after fertilization
what’s the difference between ovarian cycle and uterine cycle
ovarian cycle-> change that occur in the ovary
uterine cycle-> describes the preparation and maintenance of the uterus to receive a fertilized egg]
- occur concurrently + coordinated over 22-32 day cycle
what is the combination of the ovarian and uterine cycle called?
menstrual cycle
what is the mensural cycle regulated by
network of hormones
- hormones and their functions within the menstrual cycle
hirsutism
excessive body hair in men and women on parts of body where hair is normally absent or minimal
hyperandrogenemia
abnormally high androgen levels in the blood
what is the diagnostic criteria for PCOS
2 out of 3 of these:
- menstrual dysfunction such as lack of periods and/or cycle irregularity
- high levels of ‘male’ hormones (androgens) in the blood, known as hyperandrogenism
- the ovaries are ‘polycystic’ due to 12 or more follicles visible on an ovary
aetiology
cause, set of causes, or manner of causation of a disease or condition
what happens with PCOS
- excess androgen release prevent normal follicular development and ovulation, and also causes the development of the observed secondary male characterisits
what is the pathophysiology of PCOS
- thecal cells are involved in excess androgen production due to abnormal genetic expression
- LH hormone is excreted in excess from the pituitary and drives theca cell androgen production
- FSH levels remain in the normal stage, and can even be reduced
what is puberty
period of time during which the final physiological changes required for the full
maturation of the reproductive system take place. This period marks the activation of gametogenesis,
the production of high quantities of sex hormones, and the resulting physiological changes, such as the
development of secondary sexual characteristics.
what systems are gonads part of
both endocrine and reproductive
when does the production of sex hormones increase
- once the gonads receive a “start” signal at puberty.
- signal comes from the brain, specifically from the hypothalamus and pituitary glands
regulatory center for the endocrine system
The hypothalamus and pituitary gland
hypothalamic-pituitary-gonadal axis (H P G axis).
The hormonal pathway regulating the maturation and function of the reproductive system
hypothalamic-pituitary-gonadal axis (H P G axis is a major
major signaling pathway between the hypothalamus, pituitary gland, and the gonads
hormones in the HPG axis
- Gonadotropin Releasing Hormone
- Luteinizing Hormone and Follicle-Stimulating Hormone
- Hormonal Effects
Gonadotropin Releasing Hormone
At around 10-12 years of age
neurons in the
hypothalamus receive the signal to start producing Gn R H, which induces the
release of gonadotropins.
once Gn R H is released
it travels towards the anterior pituitary and binds secretory cells (gonadrotropes), causing them produce gonadotrophins
Two of the most relevant gonadotropins
e luteinizing hormone (L H) and follicle-stimulating hormone (F S H
In males, the H P G axis is mainly involved
the regulation of testosterone
production and the process of spermatogenesis
In females, the HPG axis is mainly involved
d in the
regulation of the menstrual cycle
In both males and females, G n R H is released from the
hypothalamus in a pulsatile manner
The frequency and size of the G n R H pulses determine
determine the synthesis and secretion of gonadotropins,
which will in turn determine the synthesis of sex hormones in the gonads
In males, G n R H pulses
have a relatively constant frequency throughout the day;
G n R H pulses females
the frequency of the pulses varies depending on the stage of the menstrual cycle
The frequency and amplitude of G n R H pulses are critical for
normal gonadotropin release
important reason for the G n R H secretion in a pulsatile manner
r is to avoid the down-regulation of the
G n R H receptor in the pituitary, maintaining the heightened sensitivity of the receptor
The release of Gn R H is self regulatory via
a negative feedback signal from the gonads
Inhibin
is a protein secreted by granulosa (female) and Sertoli (male) cells in response to FSH
accumulation.
Inhibin major action
negative feedback control of pituitary F S H secretion. inhibin down regulates F S H synthesis and F S H secretion.
The menstrual cycle consists of
the ovarian and uterine cycles
what are the ovarian and uterine cycles closely regulated by
hormones of the HPG axis
hormones of the follicular phase
- FSH
- FH
- ESTROGEN
FSH - follicular phase
- levels continue to rise from the last few days of the previous menstrual
cycle and peak during the first week
what does the rise in FSH in follicular phase stimulate
five to seven primary
oocytes to begin their maturation
what does FSH in the folliculr phase induce
proliferation of granulosa cells in the follicles, the
production of inhibin, and the expression of L H receptors on theca cells.
LH in the follicular phase
binds to the L H receptors on theca cells to induce the production of estrogen precursors, which diffuse into the neighboring granulosa cells.
: Before L H levels increase
one, or occasionally two, of the developing follicles emerge as
dominant.
what does FSH bind in the follicular pahse
F S H binds granulosa cells to produce
estrogen from these precursors
estrogen in the follicular phase
leads to a slight decrease in the levels of L H and F S H, causing the atresia of the other recruited follicles.
Thus, only one of the follicles will prevail and reach maturity, containing a mature oocyte.
hormones of the ovulatory phase
Estrogen
L H:
Estrogen: ovulatory phase
Estrogen continues to rise as the follicle matures. Estrogen exerts a positive feedback action
on the anterior pituitary to cause a surge in L H secretion.
what does the increase in LH cause the mature follicle to do in the ovulatory phase
rupture, releasing the oocyte into the oviduct
factors are involved in the mechanics of follicular rupture
proteolytic enzyme activity,
ovarian smooth muscle contractions to increase intrafollicular pressure, and vascular alterations of
perifollicular vessels
hormones of the luteal phase
FSH and LH
what to the FSH and LH cause in the luteal phase
cause the now empty follicle to transform into the corpus luteum
what does the corpus luteam inhibit
production of FSH and LH because it releases progesterone and some estrogen
not fertilization in the luteal phase will cause
corpus albicans and falling levels of progesterone and estrogen leading increased FSH levels
he uterine cycle has three phases
menses, proliferative phase, and secretory phase
Menses
- where the cycle restarts
Menses- if implantation does not occur
the decrease
in estrogen and progesterone production seen at the end of the luteal phase causes endometrial
growth to cease
- will cause sheding of uterine lining
prostaglandins
cause rhythmic contractions of the
myometrium, helping to dislodge the uterine lining. and constrict blood supply and result in tissue death
Proliferative phase
the endometrium consists of only a few layers of cells and is less than 1mm thick.
- Estrogen secretion increases due to the newly developing follicle, causing the repair and growth of the endometrium
Secretory phase
, the uterine endometrium is receptive to implantation
what phase does the proliferative phase coincide with
the latter part of the ovaran follicular phase
what phase does the secretory phase coincide with
luteal phase of the ovaries
secretory phase- progesterone
increases the blood supply to the uterine lining, and reduces the
contractility of the smooth muscle in the uterus. If no implantation occurs, the uterine lining is shed
and the cycle restarts
LH in males
enters the testes and stimulates the interstitial Leydig cells to make and release testosterone into
the testes and the blood
Follicle Stimulating Hormone males
F S H enters the testes and stimulates Sertoli cells to produce androgen-binding protein (A B P) and
inhibin.
A B P
protein that specifically binds testosterone to help concentrate it in the luminal fluid
of the seminiferous tubules, while inhibin will go to the pituitary gland and downregulate F S H
production.
The male hormonal pathway is regulated via
negative feedback system
rising levels of testoerone and inhibin males
act on the hypothalamus and the pituitary, eventually inhibiting the release of GnR H, F S H,
and L H.
Once the testosterone and inhibin levels decrease again,
the cycle restarts. This cycle repeats
between 4 and 8 times every 24 hours
f hormone disorders in men.
Hypogonadism
Gynecomastia
Hypogonadism
A condition in which a decreased production of gonadal hormones leads to below-normal function of
the gonads and retardation of sexual growth and development in children. In male hypogonadism, the
body does not produce enough testosterone, which plays a key role in masculine growth and puberty
Gynecomastia
Excessive development of the male breasts that can be caused by a variety of endocrine disorders
f hormone disorders in women
Hyperandrogenism
Polycystic Ovarian Syndrome
Hyperandrogenism
A condition characterized by an excessive secretion of androgens by the adrenal cortex, ovaries, or
testes. The clinical significance in males is negligible, so the term is used most commonly with
reference to the female.
Polycystic Ovarian Syndrome
A hormonal condition that results in infrequent or prolonged menstrual periods and the development
of small collections of fluid (follicles) in the ovaries which leads to the failure of regular egg release. You
will learn more about this condition in the next section.
