It seems daily that I am asked by clients to bring a mare into heat at a desired time to facilitate breeding, show schedules, stallion availability, synchronization with other mares, maximize early season breeding dates, or line up recipient mares with donor mares. For such a common request, and in fact, a common procedure, there are certain cases when knowing the nuisances of manipulating the length of diestrus in the mare can make or break the overall success of a reproductive cycle. In this blog article Dr. David Scofield reviews the process of short cycling mares.
In the mare, we have generally condensed the non-pregnant cycle into periods defined by either behavioral terms of estrus and diestrus or physiological terms of follicular and luteal phases. Estrus occurs over a 4 to 6 day time frame followed by a 14-16 day luteal phase of diestrus. Manipulation or shortening this luteal phase is the act of “short cycling” a mare to facilitate the needs of the breeder, the mare, or the veterinarian.
To be clear, the act of short cycling a mare means to shorten the duration of progesterone dominance produced by a functional corpus luteum (CL). For the procedure to be effective, the mare must be normally cycling, have a functional CL that is producing progesterone, and the CL must be mature or old enough to respond to the luteolytic agents available to veterinarians.
A cursory run-through of the formation of a corpus luteum is paramount to understand how we can manipulate the cycle. Two major steroid hormones are used to describe the different behavioral periods of a mare’s cycle. The first is estrogen from the cells of the dominant follicle. During the follicular phase or estrus, the dominant ovarian hormone is estradiol. During the luteal phase or diestrus, the steroid hormone produced by the CL is progesterone. Progesterone prevents a mare from showing physical signs of estrus, decreases luteinizing hormone release from the pituitary, and exerts a central calming effect on the physical activity of a mare.
Moreover, to have a functional CL, there must have been a large ovulatory follicle at some point in the previous few weeks. A normal cycle consists of a dominant 40-50 mm follicle that produces high levels of estradiol from granulosa and theca cell interactions. This follicle responds to a surge of luteinizing hormone (LH) from the anterior pituitary gland to collapse and expel the oocyte (egg), and will then refill with blood from ruptured capillary blood vessels surrounding the now ovulated follicle. This act of ovulation starts a clock. If we label the act of ovulation as day zero (0), then the average mare will be ovulating again in 21 days if she does not conceive and develop a pregnancy.
After ovulation, the granulosa cells and theca cells rearrange and mix with blood that refill the ovulated follicle to form a corpus hemorrhagicum (CH). This CH structure exists for about 24 hours and will slowly mature over the next four to five days to become a functional CL that produces increasing levels of progesterone. One interesting physiological aspect of the CL is that the same granulosa and theca cells from the original follicle undergo changes to become the large and small luteal cells that synthesize the progesterone produced by the mature CL. Although peak progesterone production from the CL is not reached until later in the luteal phase, a CL is said to be mature at five (5) days following ovulation.
This CL will persist until day 15 or 16 following ovulation before responding to natural pulses of the hormone Prostaglandin F2α (PGF2α) from the non-pregnant mare’s endometrium. These pulses of PGF2 α will cause luteolysis, or death of the CL with a resultant drop in progesterone and a return to estrus. It is this period from day 5 to 15 where we can exert some control over the length of the cycle. If a pregnancy exists the movement of the fetus will stop the natural release of PGF2 α from the uterus to prevent leuteolysis of the CL, maintaining progesterone levels. If the mare is not pregnant PGF2 α is typically administered on day 5 after ovulation in order to shorten the length of the diestrus period.
There is one more key point to mention regarding the follicular waves of follicles on a mare’s ovary. Most mares are one or two wave mares, meaning that the high circulating levels of progesterone from the CL do not affect the pulses of Follicle Stimulating Hormone (FSH) from the anterior pituitary. Therefore, a mare will still have follicles of various sizes on her ovary at different days of diestrus. As mentioned later, the size of follicles on the ovary has a profound effect on when the mare will ovulate in response to a dose of PGF2 α administered.
In the US there are two forms of PGF2 α administered to mares to cause premature regression of a mature CL. These formulations are a naturally occurring PGF2 α (Dinoprost tromethamine) and a synthetic analog designed for cattle (Cloprostenol sodium). In both cases, we administer supra-physiologic doses of the preparations. Meaning, normally a mare releases pulses of PGF2 α from her endometrium in very low levels over a period of a few hours to a day with increasing amplitude and frequency of pulses. Increasing the frequency of the pulses causes regression of the CL and a decrease in progesterone. In practice, we use one dose of PGF2 α to cause luteal regression instead of administering many small doses over hours. The benefit of a single dose administration is the ease and speed of luteolysis but some mares will experience side effects from the elevated doses used. More side effects are observed when using natural PGF2 α (Dinoprost tromethamine) versus using the Cloprostenol sodium analog.
One of my mentors in practice and in reproductive physiology had a “very large” soapbox that he would preach from occasionally. A major lesson that I learned from him was never to administer PGF2 α without having performed a trans-rectal sonogram (ultrasound) to confirm the pregnancy status of a mare and to determine the ovarian structures present prior to administering PGF2 α. This exam should evaluate ovarian and uterine structures and include the presence of a defined and organized CL, size of the accompanying follicles, and to make sure no existing pregnancy exists.
Once PGF2 α is administered in a single intramuscular dose to a mare with a mature CL, it is easy to approximate the expected day of ovulation. Most mares will enter estrus within 3 to 4 days and ovulate within 7-10 days of administration of PGF2 α.
Coupled with the fact that a CL will respond to PGF2 α at five days and she will ovulate again in 7 to 10 days makes for a total “short cycle” of 12 to 15 days. As previously mentioned, follicular waves do not stop during a normal luteal phase of the mare. Therefore, if PGF2 α is administered early in the development of a follicular wave when only 15-20 mm follicles are present, the mare will probably take longer to reach a dominant pre-ovulatory follicle and will ovulate in the later part of the window around day 9 or 10. If however, the mare has larger 25-30 mm follicle when PGF2 α is administered, she will likely ovulate earlier in the window around day 7 or 8.
If PGF2 α is administered when a large follicle is present on the ovary in conjunction with a mature CL, there are three outcomes that the veterinarian needs to be careful to monitor. Herein lies the importance of knowing what ovarian structures accompany a mature CL when a mare is administered a dose of PGF2 α.
- The follicle can ovulate within 48 hours without generating any uterine edema and the ovulation will not produce a fertile oocyte (egg).
- The follicle can ovulate once uterine edema has developed and this oocyte is fertile and can produce a viable embryo if the mare is bred to a stallion.
- The large follicle can regress, without ovulating and another follicular wave will develop to produce an ovulatory follicle in 8-10 days.
To effectively use PGF2 α to manage a cycle, I have outlined a few of the management considerations for the veterinarian and manager to discuss prior to administration of the chosen agent. Care should be used when administering PGF2 α as these agents are not only used to regress a CL but they can be used to terminate a young pregnancy, terminate later term pregnancies, cause uterine contractions, and help treat uterine infections. It is imperative to make sure the correct mare is administered the agent and only after a thorough exam to check the stage of cycle, ovarian structures, and pregnancy status of the mare. Using this reproductive technology can facilitate many of the breeding decisions we make regarding our mares. Be it to avoid a show schedule, a holiday weekend without FedEx service, synchronization of recipient and donor mares, pregnancy termination, treatment of persistent luteal states, or uterine clearance activity, understanding the uses of PGF2 α is paramount to a successful reproductive practice and breeding season.