Stress/Fertility Flashcards
What is stress?
- Stress is an individual’s perception of not coping
- Mediated by hormone prod. and this mediation depends on the duration and intensity of the stress
- Stress is known to shut down all non-essential body functions such as growth
- Decreases short-ter, reproductive ability to reproduce as in evolution, stressful situations are not a good time to have a baby e.g. risk of predation
- Avoids wasting resources on germ cell prod. & avoids putting mother at risk as she would have to be still for intercourse/birth to occur
Acute stress
- involves prod of catecholamines e.g. adrenaline/noradrenaline from adrenal medulla chromaffin cells
- Adrenal medulla is involved in acute stress because sympathetic division of ANS exerts direct control over the chromaffin cells releasing the hormones
- Adrenaline/Noradrenaline leads to characteristic stress symptoms by acting on alpha1 Rs in BVs to incr TPR which subsequently incr HR & BP
HPA Axis
-Stress causes incr production & release of CRH by the hyp into the portal circulation
-This triggers prod of ACTH in the corticotroph cells of AP
ACTH acts on adrenal cortex, casing it to grow and stimulates prof of corticosterone & cortisol (main stress hormone)
-Cortisol provides neg FB to the hyp & AP
-Cortisol also causes neg FB on hippocampus (higher brain centre) which affects mood
Natural hypogonadotrophic hypogonadism
- GnRH suppression causing low LH/FSH
- improves long-term reproductive fitness
- Common for placental mammals to exhibit reproductive hierarchies–> only one alpha/dominant pair
- All subordinates exhibit NHH, subtle bullying from dominant animals causes stress which leads to incr cortisol prod in subordinates = decr fertilit
- Subordinate males have lower plasma corticosterone –> suppresses testicular function
- Postulated that dominant males are resistant to the anti-fertility action of glucocortiocoids
i. e. it is stressful being the dominant male but they can cope
Chronic stress
Hypothalamic amenorrhoea
Exercise-related amenorrhoea
- Can cause infertility as HPA interacts with HPG
- Hypothalamic amenorrhoea:
- ~30% cases have psychological cause
- Minor contributions from DA, 5HT, PL, CRH & Cortisol
- Major mediator = incr opiates –> endorphins
- Exercise-induce amenorrhoea:
- Incr CRH, cortisol & endorphins (drives addiction)
- complex metabolic adaptations to maintain glucose but spare muscle
- incr sensitivity to insulin
- decr sensitivity to IGF-1 (no longer stim. GnRH)
- Young athletes are vulnerable
Effects of stress on Dopamine?
-DA levels generally increased in stress but its actions via the D2 receptor are decreased
-DA usually acts on D2 receptor on lactotroph cells of AP to inhib prolactin secretion
-Loss of DA means prolactin output isnt suppressed
-hyperprolactinaemia = dcr libido (to prevent another child being conceived during breastfeeding)
-Also suppresses GnRH secretion –> lactational amenorrhoea
PL decr sensitivity of g/troph cells to GnRH & blocks LH surge response to E2
-DA activity decreased so unable to stim. extra-hypothalamic nucleus accumbens to prod libido
-elevated DA output from TID A neurons infringe & suppress GnRH neurons leading to amenorrhoea/infertility
Effects of Stress on Serotonin
- Stress causes upregulation of Tryptophan hydroxylase which increases the rate of production of serotonin
- Serotonin causes hyperactivity of the HPA axis leading to incr CRH > not only incr cortisol byt also acts to incr serotonin levels via pos FB mechanism
- lack of neg FB means cortisol prod is unrestrained
- Elevated 5HT suppresses sexual responsiveness in both sexes –> in cats, lordosis is seen (back arch)
How does stress incr B-endorphin levels?
- Stress incr expression of POM-C, a pre-cursor polypeptide which is cleaved to produce peptide hormonr ACTH & opioid peptide B-endorphin
- Incr ACTH acts on adrenal cortex to further incr cortisol prod and exacerbate stress response
Explain B-endorphin structure and how it acts on its receptor
- 32aa peptide fragment produced by post-translational modification of C-terminal of POM-C, it is a major mediator of stress on fertility
- Works via redundancy- cannot fail as it has so many mechanisms
- Expressed inpituitary corticotrophs & hypothalamic opioderic neurons of the Arc
- It is an opiod, acts on u-opiod receptor -> proved by using different opioid recepter agonists on rat pituitary
- deltaR= no effect on basal LH output, did decr GnRH response
- KR=incr basal, no effect on GnRH response
- uR= decr both basal LH & GnRH stimulated LH output
- in socially subordinate primates, Naloxone (u-opioid antag) incr GnRH, LH & FSH prod and animal is able to reproduce again
how does B-endorphin suppress pulsatile GnRH secretion from GnRH neurons?
what else does it do?
- Hyperpolarises GnRH neurons to suppress GnRH secretion
- Opens GIRK channels
- has indirect effect by incr GABA
- GnRh secretion= dependent on NO & PGE2
- BEndorphin disrupts GnRH secretion in two ways
1) Usually, L-Arg is converted into NO via nNOS –> B-Endorphin inhibits nNOS (first hit)
2) NO causing increased PGE2 is inhibited by GABA –> B-endorphin indirectly increases GABA, depressing PGE2 levels and so decreasing GnRH secretion - Also increases D2 secretion from TIDA neurones as a secondary back up suppression system
- Acts on pituitary to make g/trophin cells unresponsive, preventing all LH output
- Has receptors on MPOA where it works to suppress copulatory behaviour
Glucocorticoids cause interaction of HPA with HPG such that HPG axis is inhibited at every level, how?
- Cortisol has effects on GnRH (hyp), LH/FSH (Pit) & E2,P,T (gonads)
- Acts at hyp to suppress GnRH (less than BE)
- ICV injection of cortisol into Arc/MPOA suppresses LH (not FSH)
- central effects of GCs & CRH are antagonised by naloxone
- acts on gonads to suppress LHCG/FSHr expression
- Also inhibits LHCGr/FSHr signalling and steroidogenesis
- Inhibit leydig cell prod of T
- inhibits ovarian pregnenolone prod (precursor for all steroid hormones)
What does 11BHSD do?
- Tissues have varying sensitivities to cortisol due to expression of 11BHSD
- 11BHSD1 converts inert cortisone into active cortisol
- 11BHSD1&2 does the opposite
- cells have varying sensitivites due to varying 11BHSD levels - balance of 1&2?
How does 11BHSD affect female fertility?
- 11BHSD is expressed in oocytes to inactivate cortisol and prevent it affecting oocyte maturation/fertility
- As eggs mature they have incr 11BHSD activity - provides resistance to damaging effects of GCs (Can cause apoptosis via activation of Fas/FasL system)
How does 11BHSD affect male fertility?
- 11BHSD enzymes are expressed & active in boar & rat epididymus - implicates GCs in offence against epididymal sperm maturation
Effects of cortisol on oocyte
Dexamethasone
Restraint/Predatory Stress
- cortisol & corticosterone can stim GVBD in fish oocytes, unlike mammals
- Dexamethasone (cortisol agonist) inhibits GVBD req for egg maturation in pig embryos- caused by suppresion of cyclinB1
- Dexamethasone & cortisol have little effect on GVBD in murine embryos but inhibit progression from meiosis I & II in studies conducted under mineral oil
- restraint stress & predatory stress impair ovulation & oocyte development potential in mice in vivo - cannot be replicated using cortisol in vitro
