Reproductive systems and gametogenesis Flashcards
Hypothalamic-pituitary-gonadal axis
Part of the endocrine system
Endocrine glands secrete hormones into bloodstream which travel + act on target organs
Axis
Multiple endocrine glands working together as a system to regulate development, reproduction + ageing
Hypothalamus
Component of the forebrain that regulates many core body functions
What functions does the hypothalamus regulate?
Metabolism
growth
reproduction
stress
What peptide hormone does the hypothalamus release?
Gonadotrophin releasing hormone
GnRH
What cells make up the anterior pituitary?
thyrotropes
somatotropes
gonadotrophs
corticotropes
lactotropes
Thyrotropes
TSH
Somatotropes
Growth hormones
Gonadotrophs
FSH
LH
Corticotropes
ACTH
Lactotropes
Prolactin
Gonadotrophin releasing hormone
stimulates gonadotroph proliferation and hormone production
sets up signalling cascades that cumulate in expression of FSH/LH
What stimulates gonadotrophin release?
Increased calcium
What happens when FSH/LH stimulate the ovaries/testes?
produce steroid hormones
oestrogens and androgens
What are the three main types of sex steroid?
progestagens
androgens
oestrogens
What precursor are all sex steroids derived from?
cholesterol
What is the action of sex steroids dictated by?
tissue-specific receptors
What are the sex steroids essential for?
reproduction
gametogenesis
maintenance of secondary sex characteristics
Inhibin and activin
bind to specific receptors on gonadotrophs
exert opposing actions on FSH expression
inhibin modulates activin activity
What family are inhibin and activin part of?
TGF-beta
Consequences of gonadal atrophy
destruction of GnRH neurons
generation of genetically null GnRH mice
immunisation against GnRH peptide
How is GnRH released?
pulsatile manner
pulses begin at puberty
controlled by pulse generator in hypothalamus
How can alterations in the output of LH/FSH be achieved?
increasing/decreasing amplitude or frequency of GnRH pulses
modulating response of gonadotrophs to pulses
Kisspeptin
positive regulation og GnRH secretion
master player of control of reproduction
encoded by kiSS1
What does kisspeptin do?
binds to GPR54 receptor found in all GnRH neurons
potent GnRH stimulator
receptor found in many tissues
kiSS-1+ neurons
direct targets of steroid hormones
binding results in negative feedback of kisspeptin and therefore GnRH
RFamide-related peptide (RFRP-3)
negative regulator of GnRH secretion
mammalian orthologue of gonadotrophin inhibitory hormone
What does RFRP-3 act on?
gonadotrophs, kiss1 neurons and GnRH neurons in the hypothalamus
receptotrs also in gonads
What does RFRP-3 do?
results in reduced GnRH output
suppresses the signalling cascade within gonadotrophs that express LH/FSH
Control of puberty onset
kisspeptin-GnRH axis becomes fully activated- pulse generator mechanism allows pulsatile release
metabolic gating
What role does leptin have in puberty onset?
necessary for puberty to proceed but isn’t sole requirement
acts on GnRH neurons indirectly
Spermatogenesis
the production of spermatozoa from spermatogonial stem cells
Testes
houses seminiferous tubules, the site of spermatogenesis
temperature important
Epididymis
sperm storage and maturation
Vas deferens
transport of sperm from epididymis to urethra during ejaculation
Seminal vesicle
produces a mucus secretion which aids the mobility of sperm
Prostate gland
produces an alkaline secretion that neutralises the acidity of any urine in the urethra and aids the mobility of sperm
Urethra
tube that carries urine and sperm out of the body
What are the two functions of the testes?
produce androgens and other hormones for sexual differentiation
produce spermatozoa for sexual reproduction
Structure of seminiferous tubules
coiled tubules lined with seminiferous epithelium
site of spermatogenesis + location of sertoli cells
What does the stroma of testes consist of?
blood vessels, lymph and leydig cells
Leydig cells
in stroma
synthesize and secrete steroid homrones
Primordial germ cells
gamete precursors
identifiable at 3 weeks gestation
What is the fate of PGCs as gestation goes on?
expands by mitosis and migrates to the genital ridge primordium
a second set of cells migrates in germinal epithelium which will become sertoli/granulosa cells
Spermatogenesis overview
begins at puberty, produces 100 million a day
involves mitosis and meiosis
What is the final differentiation step of spermatogenesis called?
spermiogenesis
What does spermatogenesis produce?
4 mature spermatozoa
identical in size but not genetically
Spermatogonial stem cells
adult stem cells
self-regenerating pool undergoing rounds of mitosis
groups of morphologically distinct cells emerge- A and B
Type A spermatogonia
produce a clone of 16 cells which enter further rounds of mitosis with some differentiation in between
Type B spermatogonia
go on to become primary spermatocytes
Spermiation
fully differentiated sperm released into the lumen
Acrosome cap
important for fertilisation
formed by golgi apparatus
Tail
required for motility
formed by one of centrioles elongating
Mid-piece
contains the mitochondria
Central axoneme
made up of bundles of fibres
What changes take place during spermiogenesis?
nucleus changes to fit into sperm head
cytoplasm and organelles removed by sertoli cells via phagocytosis
golgi apparatus → acrosome cap
centriole elongation → tail
Effects of spermatogenesis on transcription
X and Y chromosome transcription stops before meiotic divisions
autosomal transcriptional activity ceases during spermiogenesis
Chromatin remodelling in spermatogenesis
histones replaced by protamines
tightly compressed compressed chromatin with no gene expression
Blood-testis barrier
barrier to macromolecules formed by sertoli cells tight junctions
separates testes into basal and adluminal compartments
When do spermatogonia become spermatocytes?
once they enter meiosis and move away from the basement membrane
cross into adluminal compartment where they receive all nutrients from sertoli cells
Adluminal compartment
immune-privileged site
protects haploid cells from potential immune rejection
Duration of spermatogenic cycle
every section of seminiferous tubule produces sperm every 16 days
Spatial and temporal organisation of spermatogenesis
set lag time between development of clones
different sections of tubule- different stages
gap junctions between sertoli cells provide communication
Passage through epididymis
takes 5-11 days
sperm acquire potential to swim + fertilise oocyte (dependent on androgens)
Where are mature sperm stored?
in the tail end of the epididymis ready for ejaculation via the vas deferens
Activin A in spermatogenesis
positive feedback on pituitary FSH production
autocrine effects on sertoli cells
paracrine effects on spermatogenic clls
Inhibin B in spermatogenesis
stimulatory effect on leydig cells
negative feedback on FSH production
acts as activin antagonist
indicative of sperm count
Prolactin in spermatogenesis
enhances LH stimulation of leydig cells
Oestrogen in spermatogenesis
required for fluid absoprtion in testes
Oxytocin
stimulates seminiferous tubule motility
What are steroids converted to in the testes?
more potent dihydrotestosterone
or oestrone + oestradiol 17B
What do the hormones produced from steroid conversion do in sperm?
act to stimulate sertoli cells
also secretes into the blood or tubular fluid
What is testosterone essential for in sertoli cells?
maintenance of blood-testes barrier
sertoli-spermatid adhesion
spermatid elongation
spermiation
production of testicular fluid
What does testosterone do in the tubule lumen?
binds to androgen binding proteins secreted by sertoli cells
complex travels to + stimulates ducts of testes
Testosterone in leydig cells
acts autocrinologically in a negative feedback loop
During spermatogenesis which cell type are the first to become haploid?
primary spermatocytes
What are the key hormones acting in the male reproductive system?
testosterone + oestogen
activin A and inhibin B
FSH and LH
GnRH
prolactin
oxytocin
Oogenesis
production of oocytes from primordial germ cells
Uterus
supports pregnancy
Ovaries
produce oocytes and secrete hormones
Ovarian stroma
connective tissue, smooth muscle, stromal cells and developing follicles
Uterine tube
connects ovaries and uterus
important for transport of oocyte/embryo
Two main reproductive functions of the female genital tract
gamete production and transportation
site of implantation and support of foetal development
How does the episodic nature of the menstrual cycle facilitate its functions?
first oestrogenic half- matuer oocyte produced + ready for fertilisation
second progestagenic half- uterus made ready to allow implantation + support pregnanct
How does adult ovarian function differ from testicular function?
far fewer oocytes produced
ovulation occurs episodically ratehr than continuously
ovulation stops at menopause- sperm production declines but continues
What are the timings of oogenesis in general?
mitotic divisions all occur during foetal development
girls born with primary oocytes arrested at prophase I
resumption of meiosis + oocyte development occurs after puberty
Products of meiosis II in oocytes
asymmetric
produce one mature oocyte and two polar bodies that contain chromosomes but little cytoplasmic material
Stages of follicle development
primordial follicle → preantral follicle → antral follicle → preovulatory follicle
What is the follicle?
provides appropriate supportive environment for a developing oocyte
female version of seminiferous tubules supporting sperm development
Primordial → preantral follicle
mRNA + rRNA
large amounts produced to build organelles and generate protein stores
Primordial → preantral follicle
granulosa cells
proliferate to form thick layer around oocyte
contact between granulosa cells and oocyte maintained through cytoplasmic processes
Primordial → preantral follicle
glycoproteins
secreted by oocytes
condense to form the zona pellucida
Primordial → preantral follicle
ovarian stromal cells
condense to form the thecal layer
seperated from granulosa layer by membrane propria
Antral follicle development
thecal layer expands and further develops to form two layers: theca interna and externa
granulosa cells secrete flluid
increasing follicle size due to antrum
oocyte continues to synthesise RNA + make proteins
Cumulus oophorus
granulosa layer that surrounds the oocyte
suspended in follicular fluid by a thin stalk that connects to mural granulosa cells
Communication between granulosa cells and oocyte
connected via cytoplasmic processes
gap junctions between adjacent granulosa cells at oocyte surface
extensive network allows transfer of amino acids + nucleotides to oocyte
resembles sertoli cell-spermatogenic complex
How is very early primordial follicle development stimulated?
locally via growth factors and cytokines
few follicles recommence growth every day
Regulation of follicle development
dependent on pituitary after early stage
FSH- preantral
LH- antral
LH and FSH in follicle development
only cells in theca interna bind LH
only granulosa cells bind FSH
stimulate follicles to grow + eggs to mature
What is the effect of LH stimulation on thecal cells?
production of androgens androstenedione + testosterone
What is the effect of FSH stimulation on granulosa cells?
conversion of androgens from thecal cells to oestrogens
oestradiol 17B + oestrone
What is the effect of granulosa cells expressing LH receptors later in the menstrual cycle?
LH stimulation resulting in synthesis of progesterone
How is the oestrogen surge created?
increase in androgens cause granulosa cells to proliferate and increase oestrogen production
oestrogens themselves also promote granulosa proliferation
What is the purpose of an oestrogen surge?
exerts positive feedback
stimulates LH surge
Ovulation
characterised by LH surge which coincides with expression of LH receptors on granulosa cells
Effects of LH surge
entry into preovulatory phase of growth
nuclear membrane breaks down + meiosis resumes up to metaphase II
cytoplasmic maturation occurs
follicle ruptures + oocyte carried out in follicular fluid
Luteal phase
granulosa cells switch from oestrogen to progesterone production under LH stimulation
positive feedback loop- exponential increase in progesterone
What is the effect of the progesterone increase in the luteal phase?
depresses growth of less mature follicles
promotes transition to progestagenic phase of ovarian cycle
What is the corpus luteum?
the empty follicle after collapsing and becoming highly vascularised post-ovulation
secretes inhibin and oxytocin to maintain it + luteolysis
undergoes luteolysis
What do granulosa cells become and do in the corpus luteum?
large lutein cells
synthesize progestagens
What do thecal cells become and do in the corpus luteum?
small lutein cells
produce progesterone + androgens
How does oestradiol act in different ways during the menstrual cycle?
low concs- negatively regulates LH expression
high concs- positively regulates LH expression
Main effects of progesterone
enhances negative feedback of oestradiol + blocks its positive feedback
acts on both hypothalamus + pituitary
How is FSH secretion from the pituitary regulated?
increase in progesterone results in fall in FSH
activin positively regulates
inhibin B selectively negatively regulates + antagonise activin
