ICL 2.3: Spermatogenesis, Oogensis, Ovulation and Formation of Corpus Luteum Flashcards
what is gametogenesis?
the process of formation of gametes (eggs or sperm) from the primordial germ cells
the basic steps of gametogenesis are common in both males and females
what are the 4 phases of gametogenesis?
- extra-gonadal migration of origin of primordial germ cells (PGC) from the yolk sac along the dorsal mesentery of the hindgut to genital ridges (which is the future place of gonads)
- proliferation of germ cells at genital ridges by mitosis
- meiosis (reduction division from 2n to 1n) of germ cells
- structural and functional maturation of the ova and spermatozoa
what happens is the primordial germ cells don’t make it to the genital ridge from the yolk sac?
ovaries and testis will be formed because they’re a different set of cells
but if the PCGs don’t get to the genital ridge then the ovaries and testis won’t have eggs or sperms
sometimes the PCGs will get to one side so then you’ll only have sperm from one testicle or eggs from one ovary
what is spermatogenesis?
the formation of spermatozoa from the primordial germ cells (PGCs)
once the PGCs arrive at the genital ridge of a male embryo, they become incorporated into the sex cords –> sex cords then form the seminiferous tulles and the epithelium of the seminiferous tubules differentiate into Sertoli cells which product MIS
once the PGC get to the genital ridge, they stay there till puberty!! they don’t do anything before that
where are Leydig cells located?
in-between the seminiferous tubules
they produce testosterone
what is the path of sperm from the testis to ejaculation?
sperm is made in the seminiferous tubules –> it gets emptied into the retentions testis –> efferent ducts –> epididymis –> vas deferens
what is the function of epididymus?
the storage and maturation of the spermatizoa
it produces nutrients to make sure the sperm grow
what is the site of spermatogenesis?
seminiferous tubules
what are the stages of sperm formation?
spermatogonia (2n) –> primary spermatocytes –> secondary spermatocytes –> spermatids –> spermatozoa
what are the different cells found in the seminiferous tubules?
- spermatogonia (2n) –> primary spermatocytes –> secondary spermatocytes –> spermatids –> spermatozoa
- sustentacular/Sertoli cells
* Leydig cells are outside the seminiferous tubules
what is the blood testis barrier?
the Sertoli cells have cytoplasmic extensions between them connecting them –> Sertoli cell processes from 2 Sertoli cells create a membrane ( barrier) between spermatogonia and primary spermatocytes. -This barrier is known as blood testis barrier, BTB.
spermatogonia are present at the basement membrane –> then on top of them the next layer is the 1 spermatocytes –> 2nd spermatocytes –> spermatid –> sperm and it is ALWAYS in this order from the bM to the lumen of the seminiferous tubule
so the BTB is Sertoli cells between the spermatogonia and the 1 spermatocytes
what is the function of the blood-testes barrier?
- BTB controls which substances are transported from blood to spermatocytes/ spermatozoa and which substances are excluded
if there’s a toxic substance in the blood, sperm is really susceptible to them and the BTB keeps them substance away from the spermatocytes
- the BTB also prevent an auto-immune reaction against the spermatozoa –> the spermatogonia are present in fetal like which the cells past the BTB aren’t present till puberty –> so since spermatogonia have been around since fetal life, they are recognized as self but since spermatocytes, spermatids and spermatozoa form at puberty, the body doesn’t recognize them as self and they would be attacked without the BTB and there would be no spermatogenesis
what do Sertoli cells secrete?
- Inhibin and Activin: Inhibits FSH secretion from Anterior pituitary; activin has the opposite effect and is activated when FSH levels are low
- AMH (Anti-Mullerian Hormone): regresses Mullerian duct/paramesonephric duct in male fetus during early sexual differentiation – if this doesn’t happen a female will be formed
- Androgen Binding Protein or ABP: increases local testosterone level in seminiferous tubules to aid in spermatogenesis
- aromatase enzyme: converts testosterone into 17 beta estradiol to direct spermatogenesis
what are the functions of Sertoli cells?
- phagocytosis of dead spermatozoa
- absorbing residual cytoplasm from spermatozoa before they can fertilize
- blood testis barrier to prevent contact between blood and spermatocytes and spermatogonia; the spermatogonia are outside the blood-testis barrier; they are recognised as self
- nutrients and circulating substances do not directly reach the germ cells; Sertoli cells control which substances reach the germ cells
what are the 2 broad stages of spermatogenesis?
- spermatocytogenesis
2. spermiogenesis
how many sperm do men have?
at puberty, spermatogonia (2n) divide several times by mitosis to produce more spermatogonia [1 billion Spermatogonia (2N / 2C ] –> if all 1 billion spermatogonia make sperm all at once, then a male would ejaculate like once in their life and there would be no more spermatogonia left to make spermatozoa
so what ends up happening to prevent this is that each spermatogonium divides into 2 types of spermatogonia = type A and B cells
what are type A and B spermatogonia?
type A spermatogonia serve as the stem cells which divide to form additional type A spermatogonia, and a more differentiated type B spermatogonia (which proceed to make sperm)
this is an ongoing process throughout life
creation of stem cells at each cell division ensures lifelong supply of spermatogonia
type B spermatogonia cross the BTB through tight junctions to initiate sperm production
these type B cells are the precursors of mature spermatozoa
so basically the spermatogonia split into type A and type B and type A stays dormant while the Sertoli cell BTB opens up to allow the type B spermatogonia through so that it can mature into a spermatozoa – then when you’re ready to make another sperm, the BTB will open up and allow another type B through
what is the process of spermatogenesis?
SPERMATOCYTOGENESIS
a 44XY type B spermatogonia is released through the BTB where it undergoes mitosis and is a primary spermatocytes (44XY) – they stay like this till puberty
at puberty, meiosis 1 happens and 2 secondary spermatocytes are formed (22X, 22Y)
then the secondary spermatocytes each undergo meiosis 2 and each form 2 spermatids (22Y, 22Y, 22X, 22X)
this is the end of spermatocytogenesisi!!!
SPERMIOGENSIS
then the 4 spermatids are converted into a bullet shaped spermatozoa
this process of spermatids to spermatozoa is spermiogensis and everything before is spermatocytogensis
spermatocytogenesis and spermatogenesis together are spermatogenesis
how long does spermatogenesis take?
78 days
spermatogonia –> spermatozoa
what are the steps of spermiogenesis?
progression of sperm formation from spermatid to fully functional spermatozoa
the golgi apparatus forms the acrosome (tip of the head of the sperm) while the centriole forms the tail
the mitochondria cluster under the nucleus by the tail and get used by the sperm for energy
then the cytoplasm sloughs off and the Sertoli cells endocytose them
why are mitochondrial diseases usually from the mother?
most mitochondria is lost in the cytoplasm that is sloughed off
the remaining mitochondria is used by the sperm for its own survival so it doesn’t contribute mitochondria to the egg
what are the take aways for spermiogenesis?
Human sperm cell starts out as a round cell (spermatogonium 46 XX or 46XY) with full cytoplasmic complement just like any other somatic cell but they eventually lose it
it specialized into miniaturized version because it must be mobile and penetrate the egg
it develops various structures to accomplish this task: (acrosome, midpiece, tail)
the excess residual cytoplasmic structures are removed by Sertoli cells by phagocytosis
what are some irregular sperm morphology that can lead to fertility?
- head defects
- acrosomeless sperm
- mid-piece defects
- tail defects
which hormones control spermatogenesis?
- GnRH
- LH
- FSH
- ABP
- testosterone
- inhibin
what is the role of GnRH in spermatogenesis?
it is released form hypothalamus acts on the anterior pituitary gland to secrete LH and FSH
without this hormone there’s no formation of sperm
what is the role of LH in spermatogenesis?
acts on the Leydig cells of the testes to secrete testosterone
what is the role of FSH in spermatogenesis?
- acts on spermatogonia to stimulate sperm production
- acts on Sertoli cells to secrete an androgen binding protein (ABP) and inhibin
ABP concentrates testosterone in the seminiferous tubules
testosterone in seminiferous tubules supports spermatogenesis.
what is the role of inhibit in spermatogenesis?
released from Sertoli cells and suppresses further FSH synthesis
what is Sertoli cello-only syndrome?
aka ferm cell aplasia
in this disease, there are only Sertoli cells but no spermatozoa within the seminiferous tubules due to lack of spermatogonia
so there’s no spermatogonia, 1 spermatocytes, 2 spermatocytes, spermatids or spermatozoa
sterility is permanent and irreversible
what are the stages of oocyte formation?
primordial follicles in the ovary are on the perimeter of the ovary and every menstrual period, 10-15 of them get active but then once 1 becomes a primary follicle
the primary follicle then forms an antrum which is a cavity filled with follicular fluid that supplies nutrients to the egg
the antrum continues to grow and the follicle moves towards the wall of the ovary and then ovulation occurs when the follicle binds to the ovary wall and ruptures and releases the secondary oocyte
how many eggs does a women have throughout her life?
fetal stage = 7 million
at birth = 4 million (due to follicular atresia)
onset of puberty = 400,000
total reproductive life = 500 eggs
menopause = no eggs
what is follicular attresia?
a normal process that occurs between fetal stage and onset of puberty
occurs due to apoptosis (programmed cell death)
follicular loss higher during 10-15 years before menopause
why do menopausal women have high FSH levels?
they have no follicles left on the ovary
therefore, no estrogen in circulation, resulting in compensatory increase in FSH because the both is confused why there isn’t any estrogen
so high FSH is a mark of infertility….
what conditions is advanced maternal age linked to?
beyond age 35 (AMA: Advanced maternal age) oocyte aneuploidy sets in
advanced maternal age is linked to:
- overall decreased egg quality:
- igh infertility
- high miscarriage
- high monosomy and trisomy fetuses
what is the reproductive cycle of women?
Oogenesis, Folliculogenesis, and CL formation occur in this specific sequence repeatedly
hypothalamic, pituitary and gonadal hormones, and local autocrine and paracrine glands play the most direct and significant roles in this process
thyroid gland, adrenal gland and other endocrine glands play important indirect supporting roles
what is the functional unit of the ovary?
ovarian follicle
what is oogenesis?
the process of formation of a mature fertilizable oocyte within a follicle (cyst-like)
oocytes are derived from oogonia in the ovarian cortex
how is an oocyte formed from a germ cell?
germ cell –> oogonium (2n) –> mitosis –> meiosis i begins but arrests at prophase I
all of this happens before birth
then after puberty when FSH is released, meiosis I is completed –> 1n secondary oocyte which arrests in metaphase II + 1n polar body –> ovulation, sperm entry –> meiosis II, fertilization –> 2n fertilized egg + 1n polar body (no role)
what is the racetrack explanation of dominant follicle selection?
10-15 follicles are stimulated
the anterior pituitary produces FSH and most of the primordial follicles get FSH so they start growing but one follicle gets more FSH because it happens to be surrounded by better support cells with more FSH receptors so it becomes the dominant follicle and goes on to get ovulated
which hormones peak throughout menstruation?
at menses there is no estrogen- producing follicle on the ovary; only eggs are present but no follicles to produce hormones
the hypothalamus senses the lack of estrogen and produces GnRH which is detected by the anterior pituitary which then makes FSH
FSH stimulates growth of follicles (12-15 follicles start the race) –> the dominant follicle accumulates higher numbers of FSH receptors –> the growing follicles produces increasing amounts of E which stops the production of GnRH
when E levels reach a peak it triggers release of LH surge and the lH surge causes ovulation
what is the 2-cell, 2-gonadotropin theory?
estrogen synthesis occurs in 2 steps, one mediated by LH and the other by FSH
STEP 1 cholesterol in external theca cells is converted into androgens by LH
STEP 2
the androgen is transported into internal granulosa cells
FSH activates aromatase enzyme in the granulosa cells which converts androgen into estrogen
what happens if GnRH release is inhibited?
this happens in Kallmann syndrome, Athlete’s triad, and hypothalamic hypogonadism
the result will be no FSH/ LH from anterior pituitary, no follicular grows and no ovulation
what if a patient is suffering from estrogen-sensitive cancer?
estrogen-sensitive cancer means the cancer grows with estrogen
so you can give aromatase inhibitors to prevent more estradiol from being made
some patients have androgen-secreting tumors on the ovary. what will happen to estrogen synthesis in these patients and how will hypothalamus respond?
lots of androgen means she’s going to produce a lot of estrogen
high androgen levels lead to high Estrogen levels, which in turn, lead to suppression of Hypothalamic GnRH, resulting in anovulation (failure of ovulation)
so again use an aromatase inhibitor to prevent this!
what is hypogonadotropic hypogonadism? how do you treat it?
a severe gonadotropin (FSH/LH) deficiency is seen in patients suffering from hypogonadotropic hypogonadism –> the anterior pituitary gland isn’t making FSH
this can lead to delayed puberty/ infertility
so, administration of FSH and LH to these patients can lead to successful stimulation of follicular development, ovulation, and restoration of puberty/fertility
after an egg is ovulated, what happens to the left over follicle?
it becomes the corpus luteum!
after ovulation the empty space is filled with a blood clot and is called the corpus hemorrhagicum which grows by granuloma cell hypertrophy
the granuloma cells get luteinized and accumulate fatty tissue and cholesterol is a precursor of progesterone which is important for supporting the egg through pregnancy
if there’s no fertilization, the CL doesn’t accumulate much fatty tissue and therefore doesn’t make a lot of progesterone because it’s not needed
luteinized CL regresses in the absence of pregnancy, and becomes a scar- like structure (white in color, known as corpus albicans)
sumarry of ovulation process?
- dominant follicle ovulation / estrogen peaks.
- follicular fluid accumulates distending the follicles
- thinning of follicular wall due to distention
- hypothalamus responds to high E2 triggering LH release
LH surges, and prostaglandins, histamine, vasopressin, and plasminogen activator are also released (inflammatory reaction)
- hyaluronic acid loosens Cumulus-oophorous- egg complex which detaches from follicle wall
- rupture of follicle extrusion of the oocyte
how is the corpus leuteum lysed?
CL attracts eosinophils and T lymphocytes which activate monocytes and macrophages
together all of these cells cause lysis of the CL and formation of the corpus albicans
