(14.5) Anestrus

Question 1

(Anestrus)

Anestrus is the absence of estrus or, more broadly, the absence of cyclicity.

Whenever an animal presents for this complaint one of your first steps, before doing anything invasive, should be to ensure she is not pregnant.

Anestrus is typically divided into the following categories

1-3. what are they?

Answer 1

1. juvenile anestrus - prior to puberty the animal is acyclic - there will be follicles but they won’t fully mature
2. nutritional anestrus
3. seasonal anestrus
4. lacational anestrus

Question 2

(Lactational Anestrus)

(Mechanism of Lactational Anestrus)

1. How lactational anestrus works is going to depend on what species you examine and under what conditions. Outside of the laboratory rodents, the phenomenon is most closely studied in what?
2. can be further divided into what?
3. In the suckled animal suppression of cyclicity relies on what?
4. In the milked animal suppression of cyclicity is releated to what?

Answer 2

1. cattle and women (WHO for contraception)
2. sucking anestrus (offsrping removes milk - most common)

milked anestrus (dairy animal where offsrping is weaned and farmer removes milk)

physiology is different in these two cases

3. daily frequency of suckling episodes by a bonded offsrping
4. energy balance (note that a suckled female who it in poor body condition will have componenets of both)

Question 3

(General hypothalamo-pituitary-ovarian physiology of the pregnant and early post-partum cow.)

During the first two-thirds of pregnancy things function pretty much as they do in diestrus: in response to periodic elevations of FSH waves of follicles emerge and regress at about 7-10 day intervals and since progesterone is high the dominant follicles can’t go through final maturation and ovulate.

In late pregnancy not only are progesterone levels high, but estrogen rises also (from the feto-placental unit). This functions to suppress FSH so follicle waves no longer emerge and the ovary (apart from the CL of pregnancy) is quiescent.

At birth, with luteolysis and passage of the fetus and placenta, both progesterone and estrogen levels fall, removing inhibitory feedback and FSH release occurs. This first FSH rise occurs within 3-5 days and thereafter at the usual pattern of FSH release at 7-10 day intervals is re-established. Successive waves of follicular growth follow, the initial one capable of giving rise to a dominant follicle by 7-10 days post-partum. So post-partum anestrus is NOT due to lack of follicular waves, it is due to defects in the attainment of follicular dominance and final maturation of dominant follicles (at least in cows).

The fate of the dominant follicles in these early waves is largely tied to the frequency of LH pulses (which we know depend on the frequency of GnRH pulses). If the LH pulse frequency can get to approximately 1/hour, then the large follicle can go through final maturation, synthesize and secrete enough estrogen to induce an LH surge and go on and ovulate. This could happen for the dominant follicle of the first wave, but in a suckled beef cow or a high producing dairy cow it usually doesn’t and this follicle becomes atretic and another wave emerges. This process continues until sufficient LH pulse frequency can be re-established.

Answer 3

sorry

Question 4

(Suckling Anestrus)

1. If you compare non-nutritionally stressed beef cows suckling a calf, to average not-terribly-nutritionally-stressed dairy cows; 30-80% of the dairy cows will ovulate when?

takes beef cows till when to have first ovulation?

If you just look at suckled animals in good body condition then the system likely works almost solely via the stimulus of suckling acting at the hypothalamus to reduce GnRH secretion (and thus gonadotropin secretion). The effectiveness depends on the total daily duration of suckling (frequency of suckling x duration of each episode). The longer that high intensity suckling is maintained, the longer anestrus persists. In fact the suckling stimulus, up to a point, doesn’t even have to be suckling, just the presence of a calf that the cow bonded to is sufficient, even if suckling
 is prevented (although inguinal contact helps). If the frequency of suckling is reduced to 2x daily, like milking, then the duration of suckling anestrus is reduced but is still greater than that seen in the milked cow.

Answer 4

1. the dominant follicle of the first wave

wave 3 on average

(So cows that are only suckled, while having far lower milk production than milked cows, have a longer lactational anestrus due to the suckling stimulus.)

Question 5

(Suckling Anestrus)

1. is it important that the mother is attached to calf?
2. In some species, decrease in GnRH secretion has to do with increase in what?

that do what?

by binding to what?

what can you give cow to decrease the duration of suckling anestrus?

3. Increased sensitivity to negative feedback inhibition by what?
4. Beef cows calving in poor body condition and/or losing significant condition following calving also have components of the “milked anestrus” physiology explained in the following section. Instead of ovulating the dominant follicle from wave 3 (3.2 on average) at about 30 days post-partum, these cows don’t ovulate till follicle wave 10.6 ± 1.2, at 70-100 days after calving.

Answer 5

1. yes - there should be a bond there
2. endogenous opiod peptides (EOP’s)

release of maternal EOPs in the hypothalamus and these suppress GnRH neurons

dynorphin/kappa opiod receptors on KNDy neurons

naloxone (an opiod antagonist) - not practical for farm use

3. by estrogen

(This may also in part be that these early follicles are less steroidogenically active and thus estrogen levels stay low to moderate (inhibitory) never getting to the high levels needed to exceed the threshold required to trigger an LH surge.)

Question 6

(Milked Anestrus)

In the dairy cow that is milked rather than suckled, and in mothers of other species that are in lower body condition, a nutritional or metabolic anestrus comes into play. Increase in growth hormone following calving drives nutrient partitioning to support lactation (i.e. cows will prioritize certain systems for energy allocation and estrous cycles and maintaining body stores rank lower on their list of priorities than does lactation). High milk production per se is not the problem, you can largely divorce the effects of high milk production from poor cyclicity (and fertility) if you can maintain the cow in reasonable energy balance. It is the inability of intake to keep pace with increased demand.

1. Multiple factors influence the time it actually takes a dairy cow to have her first ovulation after calving including parity, calving difficulties, developing a metabolic disease, heat stress, lameness, metritis and endometritis; but by far the most important is what?
2. In late pregnancy feed intake declines and cows enter what?
3. Post-partum, NEB worsens as feed intake further declines and energy requirement for lactation starts to increase. The cow cannot meet her requirements from feed intake and begins to do what?
4. worst of NEB is usually when?
5. 1st ovulation generally occurs when?

Answer 6

1. energy balance (particularly severity of body condition (BCS) loss
2. negative energy balance (NEB)
3. catabolize body tissue
4. 1-2 weeks post-partum (but this is variable)
5. 2-3 weeks after the nadir (worst) of NEB is passed

Question 7

(Milked anestrus)

1. Which cows are in the greatest negative energy balance, lose the most BCS and take the longest time to return to cyclicity due to decreased GnRH pulsatility.
2. The control mechanisms within the hypothalamus are largely those we saw in the section on nutrition - what are they?
3. These cows may have increased sensitivty to what?

Answer 7

1. Cows in poor body condition and those with lowest voluntary intake (actually generally the fattest cows)
2. induced insulin resistance due to lactational drive means glucose is not available as a fuel in the “metabolic fuels hypothesis”
3. estrogen feedback

Question 8

(Milked Anestrus)

1. Cows with low feed intake and/or catabolizing large amounts of body tissue have high circulating non-esterified fatty acids but low levels of what?

Low insulin causes what?

Along with reduced LH, low levels of cholesterol, glucose, insulin and IGF-1 decrease what?

Answer 8

1. cholesterol, glucose, and insulin

it prevents formation of growth hormone receptors on the liver so even though growth hormone is high, levels of IGF-1 stay low (the growth horjmone axis is uncoupled).

granulosa cell estrogen production in the dominant follicle and it doesn’t fully mature

Question 9

(Milked Anestrus)

1. Increased feed intake in high producing cows (even those that are in not-too-bad energy balance) increases hepatic blood flow and thus clearance of what? which causes what?
2. Low estrogen levels as a result on continued low LH (mech 1) plus 2 and 3 above means:

there is reduced expression of what?

and what else?

Answer 9

1. estradiol (and eventually progesterone), so there is lower circulating level of estrogen
2. estrus (increased silent estrus and reduced length and intensity of estrus expression)

LH surge is not induced, the follicle is anovulatory, becomes atretic and a new follicle wave emerges (though these follicles may also become cystic)

(look at p147 if this is confusing)

Question 10

(Milked Anestrus)

1. Eventually with improved energy balance…

central inhibition of GnRH pulses is lifted allowing what?

increased insulin stimulates receptors for what on liver?

Dominant follicles can now do what?

2. When it occurs, the first ovulation is still likely to be accompanied by what?

Mechanism for reduced intensity of estrus is partly explained above but may also involve what?

Answer 10

1. increase LH pulses

growth hormone (the somatotropic axis is restored)

fully mature and secrete sufficient estrogen to give an LH
surge and ovulation.

2. a silent heat and potentiall short lived CL

lack of recent progesterone priming of behavioral centers for cows with prolonged anestrus (see sheep seasonality)

(Physiology of short luteal phase is also likely identical to the premature luteolysis explanation in that seasonality section.)

Question 11

(Behavioral Anestrus)

1. In these cases there is cyclicity occurring, but the behavioral manifestation of estrus is not exhibited. These are often referred to as what?

(Social)

In some cases estrus is not expressed because of social pressures. First time fillies at stud are frequently too terrified to exhibit estrus until they gain some confidence and are exposed to a gentle stallion. Older dominant mares may also repress the behavior of young fillies.
Mate preference on the part of the female also plays a part here. It is especially noticeable in some bitches when they refuse mating by the stud dog their owners have carefully selected.

(Seasonal)

1. The first ovulation of the breeding season in sheep is often silent. This is because of what?

(Post-partum)

Cyclicity post-partum in dairy cows is often established before estrus will be displayed.
In animals suckling their young, the presence of the offspring can inhibit estrus expression.

(Juvenile)

Occasionally the first ovulation will occur without an accompanying estrus.

2. This is likely similar to what?

Answer 11

1. silent estrus
2. full expression of estrus in this species requires prior exposure (from a previous cycle) to progesterone

(The CL of this first cycle is often short-lived but the next cycle is normal with a normal expression of estrus behavior.)

2. the situation in some seasonal breeders, where lack of progesterone priming from a previous cycle means the behavioral centers of the brain do not respond to the estrogen secreted in this cycle.

Question 12

(Senile Anestrus)

In women, menopause is triggered when the number of primordial follicles declines to ~1,000.
Most domestic species do not reach this stage of life but it is certainly possible a similar thing occurs. Old mares often cycle infrequently and this may be a similar syndrome.

Question 13

(Pathological Anestrus)

1. Various systemic disorders can cause anestrus by doing what?
2. Excess cortisol secretion from the adrenal in what disease may give anestrus, as may insufficient cortisol production seen in what disease? Mostly these animals will be presented for another part of the syndrome rather than infertility.
3. What is a relatively frequently cited cause of anestrus, especially in small animal medicine. Getting an exact diagnosis can be difficult.
4. Any systemically debilitating disease may secondarily reduce reproductive function.
5. Disease directly affecting the reproductive organs can also be involved, e.g. ovarian granulosa-theca tumors in mares may present for constant estrus, stallion-like behavior or anestrus.
6. Disorders of sexual differentiation, creating intersex conditions can also cause anestrus. Examples include XO-Turner’s syndrome, XY-sex reversal, testicular feminization syndromes - androgen receptor defects and 5α-reductase deficiencies.

Answer 13

1. suppression of the hypothalamo-pituitary axis.
2. Cushing’s

Addison’s

3. hypothyroidism