57. Reproduction Flashcards
Which cells within the testes does LH stimulate and what does it make these cells produce?
Leydig Cells –> they are stimulated to produce testosterone
Which cells within the testes does FSH stimulate and what does it makes these cells produce?
Sertoli cells (in the seminiferous tuules) –> they are stimulated to produce sperm and inhibin A and B
What does inhibin inhibit?
Pituitary FSH secretion
What are the three phases of the menstrual cycle?
Follicular Phase Ovulation Luteal Phase
What does LH stimulate in the ovaries?
Oestradiol and progesterone production
What does FSH stimulate in the ovaries?
Follicular development and inhibin production
What effect does oestrogen have on the HPG axis in the follicular phase of the menstrual cycle?
It has a negative feedback effect – inhibits FSH and LH
What does the leading follicle develop into by around day 10?
Graffian Follicle
Once oestrogen reaches a certain level it switches to positive feedback. How does it do this?
It increases the GnRH secretion It increases LH sensitivity to GnRH
Define infertility.
Inability to conceive after 1 year of regular unprotected sex
What is primary gonadal failure and what effects does it have on the HPG axis?
It is a problem with the gonads The testes/ovaries don’t produce enough testosterone/oestrogen so there is no negative feedback on the HPG axis meaning that you get high GnRH, high LH and high FSH.
Describe the levels of the different hormones in the HPG axis in the case of hypothalamic/pituitary disease causing infertility.
Low GnRH Low FSH Low LH
State some of the clinical features of male hypogonadism.
Loss of libido Impotence Small testes Decreased muscle bulk Osteoporosis (testosterone has anabolic action in the bone)
State 5 causes of male hypogonadism.
Hypopituitarism Kallmann’s Syndrome (anosmia + low GnRH) Illness/underweight Hyperprolactinaemia Androgen receptor deficiency (RARE)
State some congenital and acquired causes of primary gonadal disease.
Congenital: Klinefelter’s Syndrome (XXY) Acquired: Testicular torsion, chemotherapy
What are the main investigations for male hypogonadism?
LH, FSH and testosterone (if all are low –> MRI to check pituitary problem) Prolactin Sperm count (azoospermia – absence of sperm in ejaculate; oligospermia – reduced number of sperm in ejaculate) Chromosomal analysis (check for Klinefelter’s)
What is given to all patients with hypogonadism?
Testosterone to increase muscle bulk and protect against osteoporosis
How do you restore fertility in someone with hypothalamic/pituitary disease?
Subcutaneous gonadotrophin injections – stimulates testosterone release
What is the treatment for hyperprolactinaemia?
Dopamine agonists – bromocriptine and cabergoline Pituitary surgery (though this is rarely used because medicine normally works well)
State some endogenous sites of production of androgens.
Interstitial leydig cells in the testes Adrenal cortex Ovaries Placenta Tumours
What are the main actions of testosterone?
Development of the male genital tract Maintains fertility in adulthood Control of secondary sexual characteristics Anabolic effects (muscle, bone)
Testosterone is heavily plasma protein bound and it can be converted to other hormones in various tissues. State two products that testosterone can be converted to and the enzymes responsible for these conversions.
Converted by 5-alpha-reductase to dihydrotestosterone (DHT), which acts on androgen receptors Converted by aromatase to 17-beta-oestradiol, which acts on oestrogen receptors
What type of receptors does DHT and E2 act on?
Nuclear receptors
What are the clinical uses of testosterone?
Lean body mass Muscle size and strength Bone formation and bone mass Libido and potency NOTE: it does NOT restore fertility
What is the difference between primary and secondary amenorrhoea?
Primary Amenorrhoea = failure to develop spontaneous menstruationby the age of 16 years Secondary Amenorrhoea = absence of menstruation for 3 months in a woman who has previously had cycles
What is oligomenorrhoea?
Irregularly long cycles
List some causes of amenorrhoea.
Pregnancy Lactation Ovarian failure: Premature ovarian insufficiency Oophorectomy Chemotherapy Ovarian dysgenesis (Turner’s Syndrome (45 X)) Hypothalamic/pituitary disease Kallmann’s syndrome Low BMI Post-pill amenorrhoea (if you use the pill for a long time and then go off it, it could take a while for the periods to return) Hyperprolactinaemia Androgen excess (gonadal tumour)
State some features of Turner’s syndrome.
Short statue Cubitus valgus (forearm is angled away from the body to a greater degree than normal when fully extended) Gonadal dysgenesis
State some investigations for amenorrhoea.
Pregnancy test LH, FSH and Oestradiol Day 21 Progesterone (this should be high (showing that you’re ovulating) because progesterone rises in the second half of the menstrual cycle) Prolactin Thyroid function test (both hyper- and hypothyroidism can cause problems with the menstrual cycle) Androgens (testosterone, androstenedione, DHEAS) Chromosomal analysis
What are the implications on health of polycystic ovarian syndrome (PCOS)?
Increased cardiovascular risk Insulin resistance (diabetes)
What are the criteria for diagnosing PCOS?
They must have at least 2 of the following: Polycystic ovaries on ultrasound scan Clinical/biochemical signs of androgen excess Oligoovulation/anovulation
What are the clinical features of PCOS?
Hirsuitism Menstrual irregularities Increased BMI
Describe the treatment for PCOS.
METFORMIN – insulin sensitiser CLOMIFENE – anti-oestrogenic effects in the hypothalamo-pituitary axis – binds to oestrogen receptors in the hypothalamus thereby blocking the negative feedback –> increased GnRH and gonadotrophin secretion GONADOTROPHIN THERAPY as part of IVF treatment
What hypothalamic hormone has a stimulatory effect on prolactinrelease?
Thyrotrophin releasing hormone (TRH)
What effect does hyperprolactinaemia have on the HPG axis?
It reduces GnRH pulsatility so that it is released basally all the time rather than in regular pulses It will switch off gonadal function via LH actions on the ovaries and testes
State some causes of hyperprolactinaemia.
Dopamine antagonists (anti-emetics and anti-psychotics) Prolactinoma Stalk compression due to pituitary adenoma (so dopamine can’t get to adenohypophysis) PCOS Hypothyroidism Oestrogens (OCP) Pregnancy Lactation Idiopathic
What are the clinical features of hyperprolactinaemia?
Galactorrhoea Reduced GnRH and gonadotrophin secretion –> HYPOGONADISM Prolactinoma: Visual field defect Headache
Where is tubular fluid reabsorbed and what controls this process?
Rete testis Early epididymis This is under the control of oestrogen
Where do you find oestrogen within the male reproductive tract?
Tubular fluid produced by sertoli cells
What stimulates the release of nutrients and other molecules (e.g. glycoproteins) into the epididymal fluid?
Androgens
What are the roles of these secreted nutrients and molecules?
Provide energy for the impending journey Coat the surface of the spermatozoon (to protect them from the hostile environment)
Within which part of the male reproductive tract is fluid reabsorbed and secretory products put in?
Epididymis
Why is the concentration of sperm in the vas deferens higher than further down the reproductive tract?
Further down the reproductive tract, other fluids and secretory products are added thus diluting the sperm.
Where is a vasectomy performed?
Lower end of the vas deferens
Where is tubular fluid reabsorbed and what controls this process?
Rete testis Early epididymis This is under the control of oestrogen
Where do you find oestrogen within the male reproductive tract?
Tubular fluid produced by sertoli cells
What stimulates the release of nutrients and other molecules (e.g. glycoproteins) into the epididymal fluid?
Androgens
What are the roles of these secreted nutrients and molecules?
Provide energy for the impending journey Coat the surface of the spermatozoon (to protect them from the hostile environment)
Within which part of the male reproductive tract is fluid reabsorbed and secretory products put in?
Epididymis
Why is the concentration of sperm in the vas deferens higher than further down the reproductive tract?
Further down the reproductive tract, other fluids and secretory products are added thus diluting the sperm.
Where is a vasectomy performed?
Lower end of the vas deferens
Which structures contribute to the seminal fluid?
Epididymis/testes (small contribution) Seminal vesicle (2/3) Prostate (1/3)
Why is there fibrinogen and fibrinolytic enzymes in the seminal fluid?
After ejaculation, the semen initially clots and then must be broken down
Describe the capability of the spermatozoa in the seminiferous tubule.
Quiescent and incapable of fertilising an ovum
Describe the capabilities of the spermatozoa in the vas deferens.
Capable of limited movement Limited capability to fertilise an ovum
When do sperm achieve full activity and capability achieved and what is the name given to this process?
Capacitation This occurs within the female reproductive tract
What 3 changes take place in capacitation?
Loss of glycoprotein coat Change in surface membrane characteristics (leading to acrosome reaction when in close proximity to the ovum) Whiplash movements of the tail
What are all these changes dependent on?
Oestrogen Calcium
Describe the acrosome reaction.
Spermatozoon binds to ZP3 glycoprotein on the zona pellucida Once bound to ZP3, progesterone stimulates calcium influx into the spermatozoon This results in a calcium-dependent acrosome reaction This enables an exposed spermatozoon recognition site to bind to ZP2 Once bound to ZP2, the acrosome releases its enzymes allowing penetration of the zona pellucida so that the head of the spermatozoon can enter the ovum
Where does fertilisation normally occur?
Fallopian tube
What does fertilisation result in the expulsion of?
Second polar body
The zonal reaction immediately follows fertilisation. Describe the zonal reaction.
Cortical granules release molecules that degrade the zona pellucida (including ZP3 and ZP2) This prevents further binding of other sperm This is also CALCIUM dependent
Describe how the conceptus receives nutrients before implantation.
Uterine secretions
How long is this free-living phase of the conceptus?
9-10 days
In what stage of the menstrual cycle is all of this occurring?
Luteal phase – oestrogen and progesterone are high
What does the conceptus compact to form?
8-16 cells morula
What are the two parts of the blastocyst?
Inner cell mass – becomes the embryo Trophectoderm – becomes the chorion (which becomes the placenta)
What hormonal change facilitates the transfer of the conceptus to the uterus?
Increasing progesterone: oestrogen ratio
What is a decidua?
Thick layer of modified mucous membrane, which lines the uterus during pregnancy and is shed with afterbirth
What hormone environment is required for implantation?
Progesterone dominance in the presence of oestrogen
State 2 molecules that are of particular importance in implantation. Mention which cells produce these molecules.
Leukaemia inhibitory factor (LIF) Produced by endometrial secretory glands Stimulates adhesion (attachment) of blastocyst to endometrial cells IL-11 Also released from endometrial cells and released into uterine fluid
When the trophoblast cells of the blastocyst invade the underlying uterine stromal tissue, you get a decidualisationreaction. What main changes take place in decidualisation?
Increased vascular permeability in the invasion region, associated with oedema of tissues Localised changes in intracellular composition and progressive sprouting and growth of capillaries
Which chemical factors are involved in decidualisation?
Mainly IL-11 Histamine Certain prostaglandins TGF-beta = promotes angiogenesis
What is the role of hCG and when does it peak?
Peaks at 8 weeks and is particularly important in the first 6 weeks It mimics LH by binding to LH receptors on the corpus luteum and stimulating the production of oestrogen and progesterone NOTE: hCG is produced by trophoblast cells
What change takes place after about 5 weeks?
The role of hormone production is handed over from the corpus luteum to the placenta
Describe how oestrogen and progesterone levels change throughout pregnancy.
Oestrogen and progesterone levels continue to rise through pregnancy with progesterone always being the dominant influence
What is human placental lactogen? Describe its roles.
It is a growth hormone that has prolactin like effects It is important for the growth and development of the foetus
After what point would oophorectomy have no effect on pregnancy and why?
After around 6 weeks (40 days) By this point the placenta would have taken over the role of hormone production so the ovaries are no longer needed
Which steroid precursor tends to be provided by the mother for the foetus?
Pregnenolone
Which androgen is formed by the maternal and foetal adrenals?This is used as a precursor for oestrogen production.
Dehydroepiandrosterone Sulphate (DHEAS)
Which oestrogens are produced by the placenta using DHEAS from the mother and foetus?
Oestradiol Oestrone
These two oestrogens aren’t a good measure of foetal health. Explain why.
These oestrogens are dependent on precursor production from the both the foetal AND maternal adrenals. Therefore, it is not a good measure of foetal health.
What is the main oestrogen of pregnancy? Describe how it is produced.
OESTRIOL DHEAS from the foetal adrenals is conjugated in the foetal liver to form 16-alpha-hydroxy DHEAS 16-alpha-hydroxy DHEAS is then de-conjugated in the placenta and used to produce oestriol
What can be measured to gage the health of the foetus?
Oestriol: oestradiol + oestrone levels Oestriol: total oestrogens
Describe how maternal hormones change in pregnancy.
Most hormones increase in pregnancy (the pituitary gland becomes enlarged) Hormones that increase: Thyrotrophin Corticotrophin Prolactin Growth hormone Iodothyronines Adrenal steroids PTH Hormones that decrease: Gonadotrophins hGH (because placental hGH variant increases towards term) NOTE: hGH = human growth hormone
What biochemical change is required for contraction of the uterus during parturition?
Increase in intracellular calcium concentration
Describe how oestrogen increases the chance of contraction.
Oestrogen binds to oestrogen receptors and triggers the synthesis of prostaglandins within the endometrial cells. Prostaglandins stimulate the release of calcium from intracellular stores. So oestrogen tends to increase the chance of contraction
Describe how oxytocin increases the chance of contraction.
Oxytocin binds to its receptor on the endometrial cell and opens calcium channels, allowing calcium ions to move in from outside
Describe the effect of progesterone on this contraction process.
Progesterone keeps the effects of oestrogen under control Progesterone inhibits oestrogen receptors Progesterone inhibits the production of prostaglandins
What change occurs when the foetus reaches a particular size, which is crucial for contraction to take place?
There is a switch in steroid synthesis from progesterone synthesis to oestrogen synthesis This leads to oestrogen dominance –> prostaglandin production –> calcium release from intracellular stores –> promotion of muscle contraction
What 2 hormones are involved in milk production and milk ejection?
Prolactin – milk production Oxytocin – milk ejection These both have a similar neuroendocrine reflex arc stimulated by suckling
Which structures contribute to the seminal fluid?
Epididymis/testes (small contribution) Seminal vesicle (2/3) Prostate (1/3)
What 2 hormones are involved in milk production and milk ejection?
Prolactin – milk production Oxytocin – milk ejection These both have a similar neuroendocrine reflex arc stimulated by suckling
What change occurs when the foetus reaches a particular size, which is crucial for contraction to take place?
There is a switch in steroid synthesis from progesterone synthesis to oestrogen synthesis This leads to oestrogen dominance –> prostaglandin production –> calcium release from intracellular stores –> promotion of muscle contraction
Describe the effect of progesterone on this contraction process.
Progesterone keeps the effects of oestrogen under control Progesterone inhibits oestrogen receptors Progesterone inhibits the production of prostaglandins
Describe how oxytocin increases the chance of contraction.
Oxytocin binds to its receptor on the endometrial cell and opens calcium channels, allowing calcium ions to move in from outside
Describe how oestrogen increases the chance of contraction.
Oestrogen binds to oestrogen receptors and triggers the synthesis of prostaglandins within the endometrial cells. Prostaglandins stimulate the release of calcium from intracellular stores. So oestrogen tends to increase the chance of contraction
What biochemical change is required for contraction of the uterus during parturition?
Increase in intracellular calcium concentration
Describe how maternal hormones change in pregnancy.
Most hormones increase in pregnancy (the pituitary gland becomes enlarged) Hormones that increase: Thyrotrophin Corticotrophin Prolactin Growth hormone Iodothyronines Adrenal steroids PTH Hormones that decrease: Gonadotrophins hGH (because placental hGH variant increases towards term) NOTE: hGH = human growth hormone
What can be measured to gage the health of the foetus?
Oestriol: oestradiol + oestrone levels Oestriol: total oestrogens
What is the main oestrogen of pregnancy? Describe how it is produced.
OESTRIOL DHEAS from the foetal adrenals is conjugated in the foetal liver to form 16-alpha-hydroxy DHEAS 16-alpha-hydroxy DHEAS is then de-conjugated in the placenta and used to produce oestriol
These two oestrogens aren’t a good measure of foetal health. Explain why.
These oestrogens are dependent on precursor production from the both the foetal AND maternal adrenals. Therefore, it is not a good measure of foetal health.
Which oestrogens are produced by the placenta using DHEAS from the mother and foetus?
Oestradiol Oestrone
Which androgen is formed by the maternal and foetal adrenals?This is used as a precursor for oestrogen production.
Dehydroepiandrosterone Sulphate (DHEAS)
Which steroid precursor tends to be provided by the mother for the foetus?
Pregnenolone
After what point would oophorectomy have no effect on pregnancy and why?
After around 6 weeks (40 days) By this point the placenta would have taken over the role of hormone production so the ovaries are no longer needed
What is human placental lactogen? Describe its roles.
It is a growth hormone that has prolactin like effects It is important for the growth and development of the foetus
Describe how oestrogen and progesterone levels change throughout pregnancy.
Oestrogen and progesterone levels continue to rise through pregnancy with progesterone always being the dominant influence
What change takes place after about 5 weeks?
The role of hormone production is handed over from the corpus luteum to the placenta
What is the role of hCG and when does it peak?
Peaks at 8 weeks and is particularly important in the first 6 weeks It mimics LH by binding to LH receptors on the corpus luteum and stimulating the production of oestrogen and progesterone NOTE: hCG is produced by trophoblast cells
Which chemical factors are involved in decidualisation?
Mainly IL-11 Histamine Certain prostaglandins TGF-beta = promotes angiogenesis
When the trophoblast cells of the blastocyst invade the underlying uterine stromal tissue, you get a decidualisationreaction. What main changes take place in decidualisation?
Increased vascular permeability in the invasion region, associated with oedema of tissues Localised changes in intracellular composition and progressive sprouting and growth of capillaries
State 2 molecules that are of particular importance in implantation. Mention which cells produce these molecules.
Leukaemia inhibitory factor (LIF) Produced by endometrial secretory glands Stimulates adhesion (attachment) of blastocyst to endometrial cells IL-11 Also released from endometrial cells and released into uterine fluid
What hormone environment is required for implantation?
Progesterone dominance in the presence of oestrogen
What is a decidua?
Thick layer of modified mucous membrane, which lines the uterus during pregnancy and is shed with afterbirth
What hormonal change facilitates the transfer of the conceptus to the uterus?
Increasing progesterone: oestrogen ratio
What are the two parts of the blastocyst?
Inner cell mass – becomes the embryo Trophectoderm – becomes the chorion (which becomes the placenta)
What does the conceptus compact to form?
8-16 cells morula
In what stage of the menstrual cycle is all of this occurring?
Luteal phase – oestrogen and progesterone are high
How long is this free-living phase of the conceptus?
9-10 days
Describe how the conceptus receives nutrients before implantation.
Uterine secretions
The zonal reaction immediately follows fertilisation. Describe the zonal reaction.
Cortical granules release molecules that degrade the zona pellucida (including ZP3 and ZP2) This prevents further binding of other sperm This is also CALCIUM dependent
What does fertilisation result in the expulsion of?
Second polar body
