www.ivis.org Proceedings of the Annual Resort Symposium of the American Association of Equine Practitioners AAEP Jan. 19-21, 2006 Rome, Italy www.ivis.org Reprinted in the IVIS website with the permission of the AAEP
Management of Spring Transition Peter F. Daels, DVM, PhD, Diplomate ACT, Diplomate ECAR Author s address: Keros Equine Embryo Transfer Center, Passendale, Belgium. Introduction The transition in and out of the anestrous period is a gradual process and presents us with several challenges with regard to the clinical management: estimation of the stage/depth of anestrus, estimation of the time of first ovulation and choice of treatment to hasten the return to cyclic activity. Physiology The annual rhythm of reproductive activity - In the horse the circannual rhythm of reproduction is primarily regulated by photoperiod changes. This environmental signal is translated to an endocrine signal in the pineal gland which secretes melatonin during the phase of darkness. In the mare, short day length is associated with a decrease in gonadotropin secretion and consequently a decrease in ovarian activity. The mechanism whereby gonadotropin and presumably GnRH secretion is decreased during anestrus is not well understood in mares. It has been proposed that the absence of cyclic activity is the result of a lack of positive signals, e.g. long day length, favourable climatic and nutritional conditions, the presence of a stallion. Recent data suggest that seasonal anestrus should be regarded rather as a direct/active inhibition induced by signals such as short day length, temperature, and nutrition. Mares have an endogenous circannual reproductive rhythm and the main role of seasonal clues is to synchronize the endogenous rhythm to winter and summer. The endogenous rhythm can be displaced in time (shift to the left in Figure 1) but its shape cannot be modified as such. Photoperiod is likely the only factor able to displace this sinusoidal curve. By exposing the mare to artificial long daylight before the winter solstice, the curve is displaced to an earlier date (to the left on the graph in Figure 1). Endogenous annual rhythm of reproductive activity summer winter summer winter Artificial photoperiod D J F M A M J J A S O N D J F M A M J J A S O N D J F Figure 1
While the curve is moved equally to the left for all photoperiod-treated mares, not all mares start cyclicity at the same time (Fig. 2). The length of anestrus varies among mares and for the same mare between years. This variation is due to inhibitory factors such as nutrition, body condition, weight gain/loss, social stress, temperature and reproductive history (nursing, barren). These factors exert an inhibitory effect on the onset of spring reproductive activity. Correct management of mares in winter may decrease the impact of this inhibition. Endogenous annual rhythm of reproductive activity summer winter summer winter Duration of anestrus Level of inhibition Can we lower the level of inhibition? D J F M A M J J A S O N D J F M A M J J A S O N D J F Window of opportunity Figure 2 Photoperiod - It is well accepted that in the horse photoperiod is the most important external factor that influences the circannual endogenous reproductive rhythm. Additional light exposure during winter and early spring advances the onset of ovarian activity. However, to be efficacious this stimulatory photoperiod must be started after a sufficiently long period of short days and starting long daylight on Nov 1 does not result in an earlier onset of cyclicity compared to starting on Dec 1. The intensity or brightness of the artificial light was previously believed to be 100 lux. Experiments done at the INRA institute in France suggest that a light intensity around 10 lux (the equivalent of a 50 watt bulb per stall) is sufficient to make the mare believe it is daylight. The effective duration of daylight appears to be around 14.5 h but rather than the total number of hours of light in a day it is the duration of the dark period (sunset to sunrise) that is the determining factor. Mares placed in darkness during 9.5 hours, then exposed to light for 1 hour and returned to natural darkness until dawn respond in the same fashion as mares exposed to 14.5 h uninterrupted light. In practice, it is recommended to exposed mares to 2 h of light starting 9 h after the onset of darkness. Artificial long days during winter are not stimulatory as such but rather transmit a signal. Only 35 days of long days suffices to transmit the signal and tell the mare that the winter solstice has passed. This light exposure results in a shift of the curve to the left and mares exposed to only 35 artificial long days will ovulate early when returned to natural photoperiod. The average time to ovulation in mares under 100+ artificial long days and those exposed to only 35 long days is similar, about 70 days.
Temperature - In a 10-year survey of breeding records of a thoroughbred farm in Australia, the onset of reproductive activity was closely related to minimum and maximum environmental spring temperatures. The minimum and maximum temperatures in the weeks immediately prior to the first ovulation were similar in all years of the study. Field data for thoroughbred mares in the United Kingdom also suggest that the spring transition is slowed by cold weather. Thus it appears that under similar conditions of photoperiod, nutrition and management system, temperature plays an important role in the inhibition of reproductive activity. Prolactine secretion is subject to ambient temperature with secretion increasing with temperature. Experiments using dopamine-antagonists suggest that prolactine plays a role in the fine-tuning of the first ovulation possibly by stimulating the number of LH receptors on pre-ovulatory follicles. High prolactine secretion is conducive to ovulation while low prolactine secretion may delay ovulation. Thus, warm days increase prolactine secretion which stimulates ovulation. Nutrition and body condition - The effect of nutrition and body condition on seasonal reproduction has been described by several authors. Mares which receive supplementary diet of concentrates ovulate earlier than mares without supplementation. The anovulatory period is shorter in mares which gain weight during early spring. An additive effect of nutritional supplementation and artificially photoperiod has also been observed. The interval to first ovulation is longer in mares with condition score of less than 5.0 (scale from 1 to 9) compared to mares with score above 5.0. A high-energy intake shortens the interval to first ovulation in transitional mares with a low level of body fat but does not benefit mares in moderate or fat body condition. The stimulatory effect of pasture grazing on the time of first ovulation has also been reported. First ovulation occurred over a large period of time in Thoroughbred mares that were housed inside at night and were allowed to eat grass on pasture for 4-6 hours per day whereas pony mares that were kept in concrete yards during winter ovulated in synchrony after they were turned out to lush spring grass. The earlier onset of anestrus observed in young mares and the high incidence of anestrus in lactating mares may also be related to nutritional factors. While the data is scattered it seems reasonable that mares in slim to normal condition may benefit from supplementation and that mares already in good body condition do not benefit from extra energy intake. As for dairy cows, the energy balance is likely an important and care should be taken not to place overly fat mares on a restrictive diet upon arrival at the breeding farm as this may have a negative impact on her reproductive performance. Pharmacology Stimulating ovarian activity with GnRH Within the hormonal chain of command it seems logic choice to use exogenous GnRH to drive the entire reproductive axis from the top down. The major problems with GnRH treatment are the short half-life time of most GnRH preparation making and the high purchase price. The fertility of GnRH-induced ovulations and the need for continuation of treatment if the mares did not conceive are also important consideration. While several experiments using a multitude of GnRH preparations and dosage regimes have been described in the literature, none seem to have found an application in practice. Early ovulation was recently induced in transitional mares by repeating administration of a short-term, slow-release subcutaneous implant containing GnRH analogue, deslorelin (Ovuplant). It is possible that this commercially available preparation developed for cyclic mares may become of value for transitional mares.
Inducing ovulation of the first pre-ovulatory follicle in the transition period HCG and GnRH implants (Ovuplant) can be used with success to induce ovulation of the first preovulatory size follicle in the transitional period, provided that the treatment is applied when the follicle has reached 35 mm and while this follicle is still in its growing phase. This treatment is often used in addition to other management strategies. Progestogens - Progestogens have been widely used to hasten the onset of cyclic ovarian activity in seasonally anoestrous mares. There is still a debate on the effectiveness of prolonged (8-15 days) progestogen administration in anestrous mares. Some authors claim that the treatment does not affect the mean time to ovulation but rather serves to synchronize the onset of ovarian activity. Similarly to GnRH, the outcome of the treatment depends on the stage of anestrus and ovarian activity at the beginning of treatment. Daily progestogen administration does not induce ovulation in deep anestrus but ovulation occurs within 15 days after the end of treatment when applied during transition. It is recommended to administer prostaglandin at the end of treatment as some mares may ovulate during treatment. Progestogens have also been combined with estradiol but this combination does not seem more effective in inducing ovulation in anestrous mares but serves more to obtain a more tight synchronization of ovulation. Progestogens can be admistered per os (ReguMate), intramuscular injections (progesterone-in-oil) or progesterone impregnated intravaginal devices. Dopamine antagonists (sulpiride and domperidone) In anestrous mares, administration of dopamine D2-antagonists increases prolactine secretion. Studies in other species indicate that prolactine may increase gonadotropin receptors in follicles thereby making these follicles more sensitive to LH. Daily administration of domperidone (1.1 mg/kg PO) or sulpiride (0.5 mg/kg IM) results in earlier ovulation in transitional mares. The period of treatment varies depending on the stage of anestrus. In transitional mares, ovulation is induced after 12-22 days of treatment. Because the dopamine-antagonist has no influence on LH and FSH secretion, it is important to combine this treatment with a treatment that will increase gonadotropin secretion (i.e. artificial photoperiod). Combination Treatments - The reproductive management of anoestrous mares can be made more efficient when combining some of the aforementioned techniques. The first combination consists of a classic light treatment started on Dec 1 to shift the curve to the left, combined with a 14-day progestogen treatment started mid January (with or w/o estradiol), PGF2α on the last day of progesterone treatment and hcg/ovuplant when the follicle reaches pre-ovulatory to induce ovulation. This method reduces the variability of the internal from start of light treatment to first ovulation and should have the majority of mares ovulate during the first week of February. The second combination emerged from studies on the role of dopamine during anestrus. The interval from start of dopamine-antagonist treatment to first ovulation is significantly shorter when mares are placed under extended daylight. In one experiment, mares were started on long day treatment on Jan 10. Two weeks later on Jan 23, mares received sulpiride daily until the first ovulation (or for a maximum of 21 days). First ovulation in sulpiride-treated mares occurred around Feb 15 whereas mares under light only ovulated around Mar 4 (Fig. 3).
Interval to first ovulation (days) Feb 11 Jan 23 Jan 10 100 90 80 70 60 50 40 30 20 10 0 Treated -> First Ovuluation = Feb 15 Untreated -> First Ovulation = Mar 4 Pairs of equivalent mares Figure 3 Starting the light treatment on Jan 1 this treatment strategy should result in ovulation in the first week of February. Combination with a 14-day progesterone treatment as described for the first combination treatment and hcg administration during estrus may help in further synchronizing the first ovulation. Conclusion The management of the transitional mare requires an integrated approach and no single treatment is effective in inducing early ovulation. In concert with the owner, a strategy needs to be chosen and carefully implemented. Failing to do so often leads to inconsistent responses and frustration on the part of the client.