L5: Oestrous and Menstral cycles

Leanring objectives

1. hormonal changes that occur in a generalised ovarian cycle

2. similarities and differences in oestrus and menstrual cycles between animal species

3. effects of steroid hormones on the female reproductive tract and body across the ovarian cycle

4. differences between spontaneous and induced ovulation and seasonal effects in animals

Ovarian vs estrous vs menstral cycle

1. Ovarian→ what is happening the ovary→ whole cycle of hormones etc

2. oestrous→ ‘frenzy’ most mammals→ to do with the behaviour which happens at the High Estrogen levels (see image)

3. Menstral cycle→ ‘month’, humans, great apes, fruit bats and elephant shrews, Starts with mensturation (see graph)

Hypothalamic-pituitary axis→ what do the parts do

1. Kisspeptin neuron pulse generator→ Pulsation→ Feeds into GnRH

2. Kisspeptin neuron surge generator→ causes a surge in GnRh

3. Neruons act on GnRH neurons and release is a combination of these

   • After the surge→ there is a decrease in the frequency of the pulse

Feedback mechanisms in this axis

• NEGATIVE: Progesterone→ inhibit GnRH and Pulse generator

• POSITIVE: High estradiol→ increase GnRH and Surge generator

How this axis works in the menstural cycle (starting with corpus luteum)

1. Corpus luteum→ makes lots of progesterone and LH and FSH are low

2. Progesterone falls

3. pulse generator starts back at normal rate

4. increases FSH

   • critical for taking antral follicles and capturing around 20 (those that have the FSH receptor) to continue to ovulation

5. increase in estradiol and slight decrease in FSH again

6. causes generator surge

7. LH surge (also increase in FSH and decrease in estrogen)

8. Ovulation

9. Develops the corpus Luteum

10. high progesterone→Back to the same stage

How was inhibin work get incorporated into his cycle

• Forms a private inhibitory feedback system with two inhibins

  • A and B

1. inhibin B→ released by granulosa cells

   • helps reduce FSH secretion just before the estrogen surge

2. Inhibin A→ also decreases FSH

   • released during hih progesterone

How does this negative feedback (which creates this regulated cycle) maintained constant

• as long as estradiol is within the normal physiological range

  • provides relatively constant feedback during the cycle

  • one pulse per hour

When happens in e.g the menopause

• Estradiol levels drop before normal

• negative feedback is lost

see graphs were the hormone regulation is no longer constant, disordered activity

• get high levels of LH and FSH because no longer getting negative feedback from estradiol or progesterone

• pulse is 1 every 3 hours

Hypothalamic- pituitary axis male vs female

Very similar but:

Differences:

• no LH surge

• no pulse generator→ just continuous pulsating

  • if you remove the gonads

    • → high frequency LH pulses

Cyclical changes in women’s bodies

1. Endometrial changes

2. Cervical changes

3. Changes in the rest of the body

1. Endometrial changes

1. Proliferative phase

   • estrogen causes stromal thickening

   • increased surface epithelium

2. Secretory phase

   • Progesterone stimulates glands to secrete fluid rich in

     • glycoprotein, sugars and amino acids

   • Spiral artery proliferation

3. Menses

   • Shedding of endometrial lining

   • spiral arteries contract to reduce bleeding

2. Cervical changes during the cycle

• Estrogen→

  • thin mucus

  • relaxes cervix muscles

  • enhances sperm entry

• Progesterone→

  • thick mucus

  • cervix muscles firmer

  • reduces sperm entry

  • ALSO→ 0.5 degree increase in body temp 1-3 days after ovulation

Features of mucus

1. Spinnbarkeit of mucus

   • lengths to which mucus thread can be stretch before snapping

2. Ferning of mucus

   • crystalised mucus when dried on a slide shows ‘fern-like’ strucutre

3. Sperm penetration

   • in vitro test of ability of sperm to penetrate the mucus

3. Changes in the rest of the body

• most other organs have steroid receptors

• rise and fall in progesterone and estrogen give rise to premenstral symptoms in 60-70% of women

• Premenstrual dysphoric disorder PMDD

  • irritability, mood, anxiety, fatigue, concnetrtaion, eating, sleeping

• Athletic performance

  • especially in elite athletes

How does hormonal contraception work

Enhancing progesterone actions on brain and uterus/cervix

• Most use progesterone:

  1. enhance progesterone

  2. inhibits pulse generator

  3. slow the pulses

  4. hard for the reproductive cycle to stay cyclical

  5. AND→ thick mucus and muscle→ hard for sperm to penetrate the cervix

  6. A recently fertilised oocyte will not be able to implant if progesterone is around at the wrong time

i.e this shows that there is a window where progesterone is good/bad for implantation

‘ Progestins’ and ‘estrogens’

1. "Progestins" - norgesterone, desogestrel, drospirenone

2. "Estrogens" - ethinylestradiol

Estrous cycle→ in mammals e.g cats

• no menstruation

• Seasonal polyestrous induced ovulator

  1. Seasonal→ only during long days→ so can reproduce when it is warm

  2. Polyestrous→ multiple follicles going through the cycle

     • bouts of high estrogen

     • generates estrous behaviour

       • vocalize, pheromones, signalling

  3. induced ovulator→ copulation evoked LH surge

     • i.e estrous behavour→ attract male→ copulation→ LH surge

     • Causes formation of the corpus luteum

How does induced ovulation work

1. Activation of the cervix

   • e.g barbed penis

2. relay to the spinal cord

3. to brainstem

4. to the GnRH neuron and to the surge generator

What animals are induced ovulators

• cats

• rabbit

• some shrew

• koala

• hedgehog

• Camels

Special case in camels/lammas

• nerve growth factors (betaNGF) from seminal fluid

• deposited in vagina

• causes GnRH release

therefore shows there is more than one strategy to induce ovulation

Photoperiod and seasonal breeding and what stimulates hormone secretion

1. Short day breeder→ sheep (gestation= 5 months)

   • Increase reproductive activity in response to decreasing day length

   • Mate in Autumn

   • give brith in spring

   • Melatonin stimulates reproductive hormone secretion

2. Long day→ Horse (gestation= 11 months)

   • increase reproductive activity in response to increasing day length

   • Mat in Spring/Sumer and give brith in following Spring/Summer

   • Melatonin Suppresses reproductive hormone secretion

Different day length depends on how long gestation period→ preferably want the offspring during the summer

• in both cases use melatonin to affect hormonal secretion→ but melatonin response is different

How is photoperiod detected and cause this hormonal regulation (light→ pineal gland)

1. Detect light in eye and send to

2. Retinohypothalamic tract

3. to suprachiasmatic nucleus (SCN) biological clock

4. To the Paraventricular nucleus (PVN)

5. Sent back down to the spinal cord→ pre-ganglionic sympathetic axon

6. To superior cervical ganglion→ post-ganglion sympahtetic axon

7. To the pineal gland

Response once gets to the pineal (although not completely known)

1. Pineal releases melatonin

2. Melatonin received at MTRNR1A (melatonin receptor 1A) on the TSH cell of the Pars Tuberalis

3. These cells release TSH (Thyrotopin-releasing hormone) onto

4. Tanycytes

5. Tanycyte used dio2/3 (deiodinase 2/3) to convert T4→ T3

6. stimulates kisspeptin neuron pulse generator

7. This stimulates the GnRH neuron (in different ways)

   • short day= melatonin-T3 activity→ stimulates GnRH neural network

   • long day= melatonin T3 production→inhibits GnRH neuronal network→ restricts fertility to times of short T3 production

8. This connects to the Pars tuberalis just above the anterior pituitray

9. Anterior pituitary stimulates to release LH/FSH

Canine estrous cycle→ bitch

Non-seasonal, monoestrus, spontaneous ovulator

1. non seasonal→ 3 to 15 month anoestrus (depending on species)

2. spontaneous ovulator→ 2 month luteal progesterone secretion, even if not pregnacy

   • sponatenous like humans

   • high level of estrogen stimulates ovulation

   • need the behaviour attracting the mate at the right time

Generalised cycle of placental mammals

1. follicles developing

2. high estradiol

3. LH surge due to

   • spontaneous or

   • behaviour → copulation→ LH surge

4. High progesterone→ Luteal phase

there are species differences in types and durations of hormones produced

Please read

Herbison, Front Neuroendocrinol 2020

• GnRH secretion through the cycle is deterimned by summed influence of

  • estradiol-clamped

  • progesterone-regulated

  • and estradiol-regulated surge generators

• on the GnRH neuron