jones Flashcards
what is the HPG axis
The hypothalamic–pituitary–gonadal axis (HPG axis) refers to the hypothalamus, pituitary gland, and gonadal glands t regulate development, reproduction and aging
where do endocrine glands secrete hormones
into the bloodstream; the hormones travel to and act on other organs or tissues
what is the hypothalamus
part of the forebeain that regulates core (homeostatic) functions eg metabolism, growth, reproduction and stress
what is a critical component of the reproductive system that is secreted for the hypothalamus
peptide hormone gonadotrophin releasing hormone (GnRH)
anterior pituitary is an endocrine gland. made up of different groups of cells which all secrete different hormones. which cells secrete FSH and LH
gonadotrophs
gonadotroph proliferation and hormone production is positively regulated by signalling through a what
G-protein coupled receptor GnRHr
activation of G-protein coupled receptor causes gonadotrophs to secrete
FSH and LH
there are 3 main types of sex steroid. these are..
progesterones, androgens and oestrogen
all sex steroids are derived from which common precursor
cholesterol
once inside a cell, steroid-receptor complexes bind to steroid response elements on DNA and impact on transcription
T
what does oestrogen bind
oestrogen receptor on the gonadotroph
binding of oestrogen to its receptor on gonadotroph leads to what
complex translocates into nucleus and mediates negative transcriptional control of target genes through oestrogen response elements
binding of oestrogen to the oestrogen receptor on the gonadotroph leads to the reduction of what
production of FSH and LH
male and female gonadal cells express inhibins and activins what do these do
bind to receptors on gonadotroph cell and regulate FSH and LH expression
feedback control happens at the level of what
pituitary, hypothalamus or testes and ovaries
LH and FSH output is predominantly regulated by secretory products of which female organ
ovary
which secretory products from ovary exert a depressent effect on gonadotrophin output (FSH and LH)
oestrogens, progesterones and inhibins
which secretory products from ovary cause a surge on gonadotrophin output (FSH and LH)
activin, oestradiol
oestradiol acts to negatively regulate LH expression at low concs but when its at high concentrations..
it acts to positively regulate expression
progesterone has 2 effects. these are
high conc seen in luteal phase - enhances negative feedback of oestradiol
- at certain levels of progesterone, positive feedback of oestradiol is blocked
inhibins selectively negatively regulate … secretion
FSH
what cells does FSH act on
granulosa cells
what cells does LH act on
thecal cells
what is the difference in regulation of gonadotrophs in males
mechanisms similar to females except that there is absense of positive feedback in male (continual production in male)
which cells secrete androgens (mainly testosterone)
leydig cells
leydig cells secrete androgens that exerts a negative feedback response which causes a decrease in ….
GnRH
as in females, what acts at the level of the pituitary to supress FSH secretion
inhibin
GnRH is essential for gonadal function. when there is destruction of GnRH neurons what happens
gonadal atrophy
when do GnRH pulses begin
puberty
what are the 2 ways in which alterations of the output of LH and FSH can be achieved
- increasing or decreasing the amplitude or frequency of GnRH pulses
- modulating the response of gonadotrophs to the pulses
kisspeptin 1 is a 54 amino acid neuropeptide that binds to which receptor on GnRH neurons
GPR54
kisspeptin is a potent GnRH stimulator T/F
T
binding to oestrogen to kiss1 positie neurons results in…
negative feedback by decreasing GnRH expression
leptin is a peptide hormone produced by…
adipocytes
leptin levels relate to … levels
fat
leptin may be involved in activating the HPG axis at puberty via…
KISS1
leptin is necessary for what to proceed
puberty
what is spermatogenesis
the production of spermatozoa from spermatogonial stem cells
the testes are the site of spermatogenesis. what do the testes house
seminiferous tubules
what is the epididymis the site of
sperm storage and maturation
what is the vas deferens important for
transport of sperm from epididymis dueing ejaculation
what does the seminal vesicle produce
mucus secretion which aids mobility of sperm
what does the prostate gland produce
an alkaline secretion that neutralises acidity of any urine in urethra
what is the urethra
a tube that carries urine and sperm out of the body
the testis have 2 main overlapping functions
- produce androgens foe sexual differentiation
- to produce spermatozoa for sexual reproduction
testes have stroma consisting of blood vessels, lymph and leydig cells. what do leydig cells synthesise and secrete
steroid hormones
what are primordial germ cells
gamete precursors
- The PGC population expands by mitosis and migrates to the genital ridge primordium by 6 weeks gestation
T
the germinal epithelium eventually bcomes which 2 types of cells
sertoli cells (male) granulosa cells (female)
when does spermatogenesis begin and how many sperm are produced perday
begins at puberty
about 100 million sperm produced per day
what is the final differentiation step in spermatogenesis called
spermiogenesis
spermatogenesis involves mitosis and meiosis T/F
T
how many mature spermatozoa does spermatogenesis produce
4
what happens in spermatogenesis
diploid cell undergoes lots of mitotic divisions to self renew. at some point differentiates and goes down spermatogenesis route. primary spermatocytes undergo meiosis twice to generate 4 identical in size but genetically diverse spermatids
what are spermatogonial stem cells
self regenerating pool which undergo rounds of mitosis
where is it determined whether spermatogonia will divide or differentiate?
seminiferous tubules
immature sperm cells are attached to sertoli cells. where do they move when they differentiate
lumen of seminiferous tubules
what happens in spermiation
cytoplasmic bridges are broken and fully differentiated sperm are released into lumen
what part of sperm is important for fertilisation
acrosome cap
the mid piece of sperm contains the…
mitochondria
when a spermatid develops into a mature spermatozoa, what happens to the remaining cytoplasm and organelles (residual body)
removed by sertoli cells via phagocytosis
X and Y chromosome transcription stops before meoitic divisions T/F
T
when does autosomal transcriptional activity stop
during spermiogenesis
germ cell development is dependent on support from
somatic cells - specifically the nurse cells
what is transported through sertoli cells to germ cell
all nutrients
before the final maturation steps the sertoli cells play a role in what
cytoplasmic remodelling and release
when do spermatogonium become spermatocytes
once they enter meiosis and move away from the basement membrane. They cross into the adluminal compartment where they receive all nutrients from Sertoli cells
why do you need different parts of the seminiferous tubules out of sync
so you have sperm reaching maturity everyday
what cells regulate spermatogenesis
sertoli cells
gap junctions between adjacent sertoli cells provides means for…
communication
testosterone has 3 main functions in sertoli cells. these are:
- maintains integrity of blood testis barrier
- required for sertoli-spermatid adhesion
- essential for spermiation
androgens act autocrinology on leydig cells themselves in a ….. feedback loop
negative
testosterone is converted within the sertoli cells to dihydrotestosterone and …
oestrogen
FSH acts on
sertoli cells
LH acts on … cells. responsible for primary production of androgens such as testosterone
leydig
androgens act on the same cells that produce it - the ….. cells
leydig
testosterone travels to the seminiferous tubule lumen where it binds to …. produced by the sertoli cells
androgen binding proteins
testosteron-ABP travels ad stimulates the what?
ducts
testosterone and oestrogen have roles in both males and females T/F
T
mature sperm are stored in the tail end of the epididymis ready for ejaculation via the ……
vas deferens
what is oogenesis
the production of oocytes from primordial germ cells
where are oocytes produced
ovary
what does the ovarian stroma consist of
connective tissue, smooth muscle, stromal cells, developig follicles, interstitial glands
what are the uterine (fallopian) tubes important for
tranport of oocyte/embryo from ovaries to uterus
the female genital tract serves 2 main functions. these are:
- gamete production and transportation
- site of implantation; support foetal development
what is the first half of the menstrual cycle referred to?
oestrogenic/follicular
what happens during the oestrogen/follicular half of the menstrual cycle
a mature oocyte is produced and made ready for fertilisation
what is the second half of the menstrual cycle referred to
progestagenic/luteal
what happens during the progestagenic/luteal phase of the menstrual cycle
uterus is made ready to allow implantation and support pregnancy
how does adult ovarian function differ from testicular function
- far fewer oocytes are produced (mitotic divisions only take place in foetal development)
- ovulation occurs episodically rather than continuously being produced
- ovulation stops at menopause
- oogenesis has start of meiosis then arrest at prophase 1
in the luteal phase what hormone dominates
progesterone
girls are born with primary oocytes arrestted when
prophase 1
resumption of meiosis and development of oocyte in females occurs after…
puberty
asymmetric divisions in oogenesis produce 1 mature oocyte and …. polar bodies that contain chromosomes but very little cytoplasmic material
2
after ovulation when fertilisation occur ….. is completed
meiosis 2
the follicle provides the appropriate supportive environment for a developing oocyte in the same way that the ………… support sperm development
seminiferous tubules
once you get ovulation, oocyte comes out of the follicle and the follicle becomes what
corpus luteum
oocyte secretes glycoproteins which condense to form what
zona pellucida
similarly to the sertoli cell in sperm development, there is contact between the oocyte and ….
granulosa cells
granulosa cells proliferate to form a thick layer around oocyte. contact between oocyte and granulosa cell is maintained through cytoplasmic processes
T
ovarian stromal cells condense to form….
thecal layer
the thecal cells expand and further develops to form 2 layer:
theca interna and theca externa
very early primordial follicle development is stimulated locally via growth factors and cytokines. further follicle development is dependent on
pituitary
absense of pituitary input to follicles results in
atresia (degeneration)
FSH-knockout mice arrest follicular development at …. stage
preantral
LH knockout mice stop follicular development at … stage
antral
in response to FSH and LH stimulation, the follicles grow and eggs,,,,,
mature
as a result of LH stimulation. thecal cells produce what
androgens and testosterone
under the stimulation of FSH what do granulosa cells do
convert androgens produced by thecal cells to oestrogen
later in menstrual cycle, granulosa cells possess LH receptors and LH stimulation results in the synthesis of…
progesterone
oestrogens promote … proliferation
granuloa
increasein androgens causes oestrogen surge. this then exerts a positive feedback to stimulate an …. surge
LH
the LH surge causes entry into the ……… phase of growth
preovulatory
within 2 hour of the start of the LH there is a transient rise (then decline) in the output f follicular oestrogens and androgens T/F
T
after ovulation, granulosa cells switch from oestrogen production to ………. production under LH stimulation
progesterone
after ovulation granulosa are stimulated by their own progesterone leading to an exponential increase in progesterone release that is characteristic of …… phase
luteal
progesterone is essential for what to take place
ovulation
what doe the progesterone increase in the luteal phase do
depresses growth of less mature follicles, promotes transition to progestagenic phase of ovarian cycle
following ovulation the empty follicle collapses and becomes highly vascularised. it can now be referred to as the
corpus luteum
corpus luteum undergoes luteolysis. once corpus luteum is broken down you get what
the start of the new cycle
from the primary oocyte how many mature oocytes do you get
1
from one spermatocyte how many mature sperm do you get
4
sperm undergo maturation in the epididymis under the stimualtion by what
androgens
when sperm mature they acquire the ability to swim progressively. they have a more rigid flagellum and the ….. content of the tail increases
cAMP
when mature sperm enter the female tract they are not ready to fertlise. what do they have to undergo
capacitation
fully capacitated sperm exhibit 2 main characteristics. these are:
- hyperactivated motility
- changes in membrane properties that subsequently allow the acrosome reaction to happen
why must sperm undergo capacitation
- to be more responsive to signals from oocyte
- able to undergo the acrosome reaction which is essential for fertilisation
what is capacitation
- stripping or modification of surface glycoproteins
- changes in surface charge
- reduction in membrane stability through loss of cholesterol and formation of lipid rafts
how does capacitation occur
mechanisms not understood
for acrosome reaction you need capacitation but also need what
contact with the egg
the hyperactivated sperm motility caused by capacitation aids sperm peneatration of the what
zona pellucida
In humans ..% of spermatozoa do not even enter the cervix
99
oocyte and cumulus cells release what to aid sperm
chemoattractants
when does the acrosome reaction occur
after capacitation when the sperm head binds to the zona pellucida
what happens in the acrosome reation
- sperm makes contact with egg
- acrosome reacts with zona pellucida
- acrosome reacts with perivitelline space
- plasma membrane of sperm and egg fuse
- sperm nucleus enters egg
- cortical granules fuse with egg plasma membrane which renders the vitelline layer impenetrable to sperm
which part of the sperm enters egg
nucleus not the tail
the zona pellucida is composed of 4 main glycoproteins called
ZP1, ZP2, ZP3, ZP4
which zona pellucida protein is a structural protein which cross links to other zona proteins
ZP1
which zona protein contains sperm binding domain necessary for oocyte sperm recognition and penetration of zona pellucida. it is also responsible to the primary block to polyspermy
ZP2
which zona protein is involved with primary sperm egg binding
ZP3 complexed with ZP4
hyaluronidase from acrosome digests cumulus cells and exposes acrosin a proteiase on inner membrane of sperm triggering the ….. reaction
acrosome
following sperm/oocyte fusion what is released into the cytoplasm of the oocyte where it facilitates the hydrolysis of membrane bound PIP2 to DAG and IP3 triggering calcium release and oocyte activation
phospholipase C zeta
calcium pulses stimulate the resumption of what
meiosis
pronuclei come together, DNA replication occurs, pronuclear membranes break down and replicated chromosomes align on mitotic spindle ready for the first cleavage division
T
what is infertility
the inability to conceive within 1 year of trying (<35) or 6 months of trying (>35)
when men have a low sperm count what can this be referred to
oligozoospermia
low sperm mobility can be referred to as
asthenozoospermia
abnormal sperm can be referred to as
teratozoospermia
no sperm can be referred to as
azoospermia
ovulation problems can be caused by:
age hormone imbalance polycystic ovary syndrome thyroid problems premature ovarian failure
when was the first baby born by IVF
1978
what does IVF consist of
- ovarian hyperstimulation
- egg retrieval
- sperm preparation
- coincubation
- embryo transfer
sperm must be matured before IVD by the addition of appropriate factors that can stimulate ….
capacitation
when are oocytes collected in in vitro maturation
before final maturation step (follicles at antral stage)
during IVM oocytes are collected before maturation and are cultured in vitro in the presence of FSH prior to fertilisation using IVF. this means women can avoid the use of drugs which is expecially important for women with what condition
ovarian hyperstimulation syndrome (eg PCOS)
what is intra-cytoplasmic sperm injection (ICSI)
single sperm is injected directly into egg cytoplasm.
ICSI bypasses the normal events of fertilisation. sperm dont have to undergo what
capacitation
what is gamete intra-fallopian tube transfer (GIFT)
eggs and sperms combined in vitro and then inserted into fallopian tubes immediately. fertilisation happens inside body
what is zygote intra-fallopian transfer (ZIFT)
eggs and sperms are combined in vitro. wait until fertilisation occurs and embryo transferred into fallopian tubes
what is cryopreservation
freezing egg, sperm or embryo
what is mitochondrial supplementation to treat infertility called
cytoplasmic transfer
