ICL 2.3: Spermatogenesis, Oogensis, Ovulation and Formation of Corpus Luteum

Question 1

what is gametogenesis?

Answer 1

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

Question 2

what are the 4 phases of gametogenesis?

Answer 2

1. 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)
2. proliferation of germ cells at genital ridges by mitosis
3. meiosis (reduction division from 2n to 1n) of germ cells
4. structural and functional maturation of the ova and spermatozoa

Question 3

what happens is the primordial germ cells don’t make it to the genital ridge from the yolk sac?

Answer 3

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

Question 4

what is spermatogenesis?

Answer 4

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

Question 5

where are Leydig cells located?

Answer 5

in-between the seminiferous tubules

they produce testosterone

Question 6

what is the path of sperm from the testis to ejaculation?

Answer 6

sperm is made in the seminiferous tubules –> it gets emptied into the retentions testis –> efferent ducts –> epididymis –> vas deferens

Question 7

what is the function of epididymus?

Answer 7

the storage and maturation of the spermatizoa

it produces nutrients to make sure the sperm grow

Question 8

what is the site of spermatogenesis?

Answer 8

seminiferous tubules

Question 9

what are the stages of sperm formation?

Answer 9

spermatogonia (2n) –> primary spermatocytes –> secondary spermatocytes –> spermatids –> spermatozoa

Question 10

what are the different cells found in the seminiferous tubules?

Answer 10

1. spermatogonia (2n) –> primary spermatocytes –> secondary spermatocytes –> spermatids –> spermatozoa
2. sustentacular/Sertoli cells
   * Leydig cells are outside the seminiferous tubules

Question 11

what is the blood testis barrier?

Answer 11

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

Question 12

what is the function of the blood-testes barrier?

Answer 12

1. 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

2. 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

Question 13

what do Sertoli cells secrete?

Answer 13

1. Inhibin and Activin: Inhibits FSH secretion from Anterior pituitary; activin has the opposite effect and is activated when FSH levels are low
2. 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
3. Androgen Binding Protein or ABP: increases local testosterone level in seminiferous tubules to aid in spermatogenesis
4. aromatase enzyme: converts testosterone into 17 beta estradiol to direct spermatogenesis

Question 14

what are the functions of Sertoli cells?

Answer 14

1. phagocytosis of dead spermatozoa
2. absorbing residual cytoplasm from spermatozoa before they can fertilize
3. 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
4. nutrients and circulating substances do not directly reach the germ cells; Sertoli cells control which substances reach the germ cells

Question 15

what are the 2 broad stages of spermatogenesis?

Answer 15

1. spermatocytogenesis

2. spermiogenesis

Question 16

how many sperm do men have?

Answer 16

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

Question 17

what are type A and B spermatogonia?

Answer 17

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

Question 18

what is the process of spermatogenesis?

Answer 18

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

Question 19

how long does spermatogenesis take?

Answer 19

78 days

spermatogonia –> spermatozoa

Question 20

what are the steps of spermiogenesis?

Answer 20

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

Question 21

why are mitochondrial diseases usually from the mother?

Answer 21

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

Question 22

what are the take aways for spermiogenesis?

Answer 22

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

Question 23

what are some irregular sperm morphology that can lead to fertility?

Answer 23

1. head defects
2. acrosomeless sperm
3. mid-piece defects
4. tail defects

Question 24

which hormones control spermatogenesis?

Answer 24

1. GnRH
2. LH
3. FSH
4. ABP
5. testosterone
6. inhibin

Question 25

what is the role of GnRH in spermatogenesis?

Answer 25

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

Question 26

what is the role of LH in spermatogenesis?

Answer 26

acts on the Leydig cells of the testes to secrete testosterone

Question 27

what is the role of FSH in spermatogenesis?

Answer 27

1. acts on spermatogonia to stimulate sperm production
2. 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.

Question 28

what is the role of inhibit in spermatogenesis?

Answer 28

released from Sertoli cells and suppresses further FSH synthesis

Question 29

what is Sertoli cello-only syndrome?

Answer 29

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

Question 30

what are the stages of oocyte formation?

Answer 30

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

Question 31

how many eggs does a women have throughout her life?

Answer 31

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

Question 32

what is follicular attresia?

Answer 32

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

Question 33

why do menopausal women have high FSH levels?

Answer 33

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….

Question 34

what conditions is advanced maternal age linked to?

Answer 34

beyond age 35 (AMA: Advanced maternal age) oocyte aneuploidy sets in

advanced maternal age is linked to:

1. overall decreased egg quality:
2. igh infertility
3. high miscarriage
4. high monosomy and trisomy fetuses

Question 35

what is the reproductive cycle of women?

Answer 35

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

Question 36

what is the functional unit of the ovary?

Answer 36

ovarian follicle

Question 37

what is oogenesis?

Answer 37

the process of formation of a mature fertilizable oocyte within a follicle (cyst-like)

oocytes are derived from oogonia in the ovarian cortex

Question 38

how is an oocyte formed from a germ cell?

Answer 38

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)

Question 39

what is the racetrack explanation of dominant follicle selection?

Answer 39

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

Question 40

which hormones peak throughout menstruation?

Answer 40

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

Question 41

what is the 2-cell, 2-gonadotropin theory?

Answer 41

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

Question 42

what happens if GnRH release is inhibited?

Answer 42

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

Question 43

what if a patient is suffering from estrogen-sensitive cancer?

Answer 43

estrogen-sensitive cancer means the cancer grows with estrogen

so you can give aromatase inhibitors to prevent more estradiol from being made

Question 44

some patients have androgen-secreting tumors on the ovary. what will happen to estrogen synthesis in these patients and how will hypothalamus respond?

Answer 44

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!

Question 45

what is hypogonadotropic hypogonadism? how do you treat it?

Answer 45

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

Question 46

after an egg is ovulated, what happens to the left over follicle?

Answer 46

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)

Question 47

sumarry of ovulation process?

Answer 47

1. dominant follicle ovulation / estrogen peaks.
2. follicular fluid accumulates distending the follicles
3. thinning of follicular wall due to distention
4. hypothalamus responds to high E2 triggering LH release

LH surges, and prostaglandins, histamine, vasopressin, and plasminogen activator are also released (inflammatory reaction)

5. hyaluronic acid loosens Cumulus-oophorous- egg complex which detaches from follicle wall
6. rupture of follicle extrusion of the oocyte

Question 48

how is the corpus leuteum lysed?

Answer 48

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