Reproductive Cycles

Question 1

What hormones do the large follicles produce?

Answer 1

Androgens, oestrodiol, Inhibin A.

Question 2

What hormones does the the corpus luteum produce?

Answer 2

Progesterone, oestrodiol and Inhibin A.

Question 3

What does oestrogen do in the cycle?

Answer 3

• induces sexual receptivity or oestrus
• induces the LH surge
• induces uterine receptivity and gamete transport
• plays a key role in follicle selection by repressing FSH levels and inducing an increase in LH pulse frequency

Question 4

What roles does progesterone play on the reproductive cycle?

Answer 4

• has an effect on terms of priming individuals for sexual receptivity which is particularly important for seasonal breeding animals
• blocks the induction of the LH surge
• important for uterine reception and gamete transport (works in concert with oestrogen in this respect)
• maintenance of pregnancy

Question 5

One method of cycle classification is by period of receptivity. What and the 4 different cycles classified by period of receptivity?

Answer 5

1) . Polyestrous - multiple periods of receptivity as seen in the cow, pig, rodent.
2) . Seasonal polyestrous - multiple periods of receptivity around spring and summer as seen in the mare,
3) . Seasonal polyestrous short day - multiple periods of receptivity around the autumn as seen in the ewe, doe, elk and nanny.
4) . Mono estrous - one period of receptivity around April as seen in the dog, wolf, fox and bear.

Question 6

Another way of classifying cycles is by their ovulatory cycle type. Describe the 2 ovulatory cycle types.

Answer 6

Reflex or spontaneous ovulatory.

1) . Reflex ovulatory - seen in cat, ferret, mink, rabbit. In reflex ovulatory ovulation is induced by manual stimulation of the cervix during intercourse.
2) . Spontaneous ovulatory - produce and LH response to oestrodiol and thus spontaneously ovulate each cycle. In monoestrous animals such as the dog this is seasonal. In polyestrous seasonal animals such as sheep, deer and opossum this is seasonal but will occur multiple times.

Question 7

What polyestrous animals have a short cycle?

Answer 7

Rat, mouse, hamster have circadian rhythm.

Question 8

What polyestrous animals have a long cycle?

Answer 8

Cow, pig.

Question 9

What mammals have menstrual cycles?

Answer 9

Primates.

Question 10

Describe the rodent cycle.

Answer 10

Rodents have short cycles with spontaneous ovulation. The rodent cycle is divided into 4 phases.

1) . Metoestrous - like the luteal phase with progesterone production.
2) . Dioestrous - like early follicular. Small follicles with little steroid secretion.
3) . Pro-oestrous - follicular growth and oestrogen production leading to the LH surge.
4) . Oestrous - ovulation and formation of the corpus luteum.

Rodents work on a scheduled rhythm. They would normally show an LH surge in the late afternoon or early evening. They would normally show estrous at night and ovulate early the next morning. This is important in the way we utilise mouse tissue.

Question 11

Describe luteal function in rodents .

Answer 11

If there is no mating the corpus luteum functions for 1-2 days leading to a transient increase in progesterone.

On sterile mating or cervical stimulation the corpus luteum is maintained for around 2 weeks. The rodent is said to be pseudo-pregnant.

If they have a fertile mating then the normal gestation period in mice is 3 weeks.

The corpus luteum is maintained by the luteotrophic action of prolactin. This is one of the major reproductive actions of prolactin.

Ovarian progesterone is essential for the maintenance of pregnancy in the rat, mouse hamster and rabbit. This is in contrast to other models such as dogs, cats and guinea pigs where placental progesterone is sufficient to maintain pregnancy mid to late trimester.

Question 12

What is one of the main reproductive actions of prolactin?

Answer 12

The corpus luteum is maintained by the luteotrophic action of prolactin. This is one of the major reproductive actions of prolactin.

Question 13

What hormones do the small follicles produce?

Answer 13

Androgens and Inhibin B.

Question 14

Describe luteal function in domestic ruminants. What causes follicular waves? Why is the follicular phase so short in these animals?

Answer 14

Sheep are seasonal polyestrous. They have a long luteal phase and a short follicular phase and experience follicular waves.

Cattle are a aseasonal polyoestrous. They have a long luteal and a short follicular phase and follicular waves.

The theory of follicular waves relates to the fact that we have open loop feedback of the luteal phase in these species. This means that during the luteal phase we’ve got the corpus luteum pumping out lots of progesterone and blocking the control of Inhibin and oestrodiol which is coming primarily from the dominant follicle.

Therefore, you have this open loop feedback system where if you have a big dominant follicle secreting lots of oestrodiol and Inhibin that would depress FSH, but if there is no dominant follicle secreting oestrodiol and Inhibin then FSH levels will increase.

Therefore we should see an inverse relationship where we see oestradiol and Inhibin levels as an inverse wave to the pattern of FSH.

When we have no dominant follicle secreting Inhibin and oestradiol we get a high FSH concentration and stimulation of follicle development which then leads to high Inhibin and oestradiol levels and then the follicle can’t ovulate because of progesterone and the Inhibin and oestradiol levels drop and FSH rises and so on.

We get a series of fluctuations which are related to the growth or regression of dominant oestrogenic follicles.

Because progesterone is present the growing follicle can’t ovulate and it becomes atretic leading to oestradiol levels falling and FSH levels increasing (another follicular wave).

Follicles can only ovulate when the corpus luteum has regressed.

Waves of FSH have been shown to be related to follicle emergence.

The consequence of these follicular waves is that when luteal regression occurs there is often a relatively large follicle in the ovaries. That means that the duration of the follicular phase in this species is quite short as it only takes about 3 days for these follicles to grow to an ovulatory size and produce enough oestradiol to trigger an LH surge. Hence we get this situation where we have a short follicular phase and a relatively long luteal phase.

Question 15

Describe follicle selection in cattle.

Answer 15

During each of the follicular waves we get the same sort of selections events that occur during the human follicular phase.

We have recruitment that is gonadotrophin influenced, selection takes place when FSH increases.the follicle then becomes dominant and becomes LH dependent. This allows it to survive this decrease in FSH which is caused by the increased production of oestradiol from the follicle. By switching its dependence from FSH to LH it can survive and go on to dominance whilst the rest of the cohort undergo atresia.

Question 16

How long is the sheep oestrous cycle?

Answer 16

17 days.

3 days follicular and 14 days luteal.

Question 17

How long is the cow oestrous cycle?

Answer 17

21 days.

3 days follicular and 17-18 days luteal.

Question 18

Why is the follicular phase so short in domestic ruminants?

Answer 18

Due to the open feedback loop that causes follicular waves.

Question 19

Describe the lengths of the phases of the menstrual cycle.

Answer 19

The menstrual cycle is approximately 28 days and in contrast to domestic ruminants we have a roughly equal length luteal phase and follicular phase (approximately 14 days each). This is sometimes broken up with the first 5 days of the follicular phase being called the menstrual phase.

There is quite a lot of variation in cycle length between individuals.

In most women the length of the luteal phase is quite constant at around 14 days. Most of the variation occurs in the follicular phase.

The difference in length of the follicular phase in different women is due to the difference in length of time it takes different women to grow follicles and the difference in trigger points between individuals.

Question 20

Describe the menstrual cycle luteal and follicular phase. Do we have open feedback loops?

Answer 20

In contrast to domestic ruminants, during the luteal phase of the menstrual cycle we don’t have open feedback loop feedback of FSH, we have closed feedback loops.

This closed loop feedback of FSH and LH contributes to the relatively long follicular phase on that the corpus luteum in addition to producing progesterone is secreting oestradiol and Inhibin (negative feedback on FSH and LH) and that limits the growth of follicles within the ovaries during the gonadotrophin-responsive stage. FSH is maintained below threshold for the duration of the luteal phase so we generally only get the development of small antral follicles.

Emerging data from Canada is showing that approximately 16% of women do grow larger follicles during the luteal phase. However, it os not quite clear how steroidogenic these follicles are or if they are normal.

This closed feedback loop system means when we do get regression of the corpus luteum we only have these small antral follicles and it takes a considerable amount of time for women to grow a large, preovulatory follicle.

In the luteal phase we have the corpus luteum producing high amounts of oestradiol and progesterone. FSH and LH are suppressed and can’t get follicles beyond this threshold limit. They will generally grow up to become gonadotrophic responsive, stick around for a while and then become atretic. When we have luteal regression however, if the women is not pregnant we see this rapid fall in the concentration of progesterone and oestradiol in the peripheral circulation and this causes an increase in FSH in the early follicular phase. The consequence of this increase in FSH is a recruitment event. The FSH is above threshold level and this allows the recruitment of the follicle to the gonadotrophin-dependent stage where it will start to release increasing amounts of oestradiol. Eventually the oestradiol causes the FSH to be repressed and this rest of the follicles are killed off. The dominant follicle uses LH as a surrogate. The oestradiol will hit a threshold level and induce the LH surge which will cause ovulation.

This is a selection event. We have recruitment of the follicles during the late luteal phase. Selection of the follicle then occurs during the early follicular phase. Im the mid follicular phase the follicle establishes easly dominance, before becoming preovulatory during the late follicular phase.

Question 21

Describe Inhibin secretion across the menstrual cycle.

Answer 21

During the early follicular phase we see quite a big increase in Inhibin B whereas Inhibin A levels are quite low.

What happens is that the increase in FSH that occurs at the beginning of the follicular phase causes the recruitment of gonadotrophin-responsive follicles and enter the gonadotrophin-dependent stage. The follicles start secreting amounts of Inhibin B. This increasing Inhibin B starts to suppress FSH so we only get this relatively transient increase in FSH in the early follicular phase. The selection event occurs and one follicle becomes dominant. This follicle the starts to produce increasing amounts of oestradiol and Inhibin A, which further drives down FSH. We then have this transfer of dependence from FSH to LH. The dominant follicle secretes increasing amounts of oestradiol and increasing amounts of Inhibin A until we have the induction of the LH surge, ovulation, formation of the corpus luteum and in addition to progesterone and oestradiol increasing there is an increasing in Inhibin A.

Question 22

What bearing does the LH surge timing have on the probability of getting pregnant?

Answer 22

Although women don’t show estrus the probability of them becoming pregnant increases towards the time of LH surge and then drops immediately afterwords.

Question 23

Describe seasonal breeding in small ruminants.

Answer 23

The variation between different breeds of animals and breeding periods is related to the environment in which they live.

Seasonal breeding is a result of oestradiol negative feedback.

During seasonal anestrus (I.e. Summer) oestrogen is acting in an inhibitory way in terms of the sensitivity of the hypothalamus to GnRH and also the responsiveness of the pituitary to gonadotrophins. Therefore we have low levels of gonadotrophins and we only get small antral follicles and thus animals are seasonally anestrus.

The control mechanism is related to the amount of light the animal is seeing and the production of melatonin from the pineal gland in the brain.

Increased light&raquo_space;> increased firing of retinal nerves&raquo_space;> increased excitation from SCG&raquo_space;> increased inhibition of pineal gland&raquo_space;> decreased melatonin&raquo_space;> decreased GnRH&raquo_space;> decreased FSH and LH&raquo_space;> Anestrus.

And vice versa for estrus.

Question 24

Is there complete shut down of the ovaries during anestrus?

Answer 24

In most breeds of sheep there is not a complete shut down of the ovary during anestrus and the follicular waves continue unchanged.

If we can induce ovulation then we can get them to breed more often.

We can induce ovulation during anestrus by:

• stimulating pulsatile GnRH
• stimulating endogenous gonadotrophins
• exposing ewes top here on all ram effect which stimulates LH
• stress-corticosteroid mediated LH release

However fertility is still much suppressed even after induction for unknown reasons (hyperprolactinaemia?).

Sheep and similar animals won’t show behavioural estrus on the first ovulation (silent ovulation). Progesterone then primes the brain (04 from corpus luteum) and the animal will display behavioural estrus on the next ovulation.

Question 25

Describe the process of menopause.

Answer 25

Commercial animals are rarely alive long enough to deplete their primordial follicles.

I’m women from around their early 30s they begin to show endocrine changes that begin to indicate that they are starting to deplete they ovarian reserve. The ovarian reserve is usually depleted by the woman’s early 50s and she stops cycling. As the reserve is depleted there is a gradual increase in FSH.

The cause of this increase in FSH is quite simple. In a normal individual FSH is controlled by oestrodiol and Inhibin released by a large number of follicles. Towards menopause we have the same amount of oestradiol and Inhibin coming from the dominant follicle, but lower amounts from the growing follicles as there are fewer of them. This means that FSH becomes elevated.

Perimenopausal women will likely experience irregular cycles and symptoms associated with the endocrine changes. Irregular cycles may occur due to the fact that there are less follicles to recruits cycles may be anovular with no ovulatory or luteal phase when the women is hypooestrogenic. This lack of oestrogen also causes menopausal symptoms such as hot flushes etc.