A714
Reproduction - Estrous Cycle Manipulation

artificial lighting | drugs used to manipulate reproductive function | Prostaglandin PGF2a | progesterone | intrauterine placement of glass marbles | human chorionic gonadotropin (hCG) | Gonadotropin Releasing Hormone (GnRH)

Introduction: The cyclic activity in mares is often described as "reliably erratic." Management tools such as the use of artificial lighting and pharmaceutical treatments help breeders gain a limited amount of control over a reproductive system that is often difficult to predict with an acceptable amount of certainty. The average mare will cycle every 21 days and will usually stay in heat or estrus for about 4-7 days. Most mares will ovulate about 24-48 hours prior to going out of estrus. Following is information on the use of lighting and pharmaceuticals in estrus manipulation.

Artificial Lighting: In many competitive events, horses compete at 2 and 3 years of age. Since a horse born in January and a horse born in April both are considered to become 1 year old on January 1st the subsequent year, there is considerable economic pressure for breeders to produce foals that are born as early as possible to increase their chances of being competitive with the others that foaled the same year. This is why many breeders use artificial lighting to cause mares to begin cycling as early as possible during the year.

The concept behind artificial lighting management programs is based on the mare’s own natural reproductive process. Years of evolution have programmed the mare’s reproductive physiology to become dormant during the winter to prevent her from foaling at a time when grass is scarce and when the cold winter conditions could threaten the health of a newborn foal. This period of reproductive dormancy is called anestrus and is characterized hormonally by high circulating levels of melatonin that serve to suppress the hormones that drive ovarian activity.

An increase in day length, such as would naturally occur in the spring, reduces circulating melatonin and ovarian activity is gradually resumed. Fortunately, this process can be stimulated by artificial means. Research shows that cycling and ovulation will occur within 90 days after mares are exposed to an artificial lighting regimen that increases the perceived day length to 16 hours. Therefore, beginning in early December, many breeders will keep mares under artificial light from dusk until around 10 PM, throughout the winter. Their goal is to cause the mare to be capable of conceiving in February, then foaling in January the following year.

Drugs Used to Manipulate Reproductive Function: The pharmacological tools often used to influence the timing of reproductive function include prostaglandin, progestins, and gonadotropic agents. Each of these agents work in their own way to control the timing of an otherwise natural physiological process. They cause this change in a normal reproductive physiological process by stimulating or inhibiting the occurrence of an event associated with the estrous cycle.

  1. Prostaglandin PGF2a: Prostaglandin is the first drug that will be discussed. PGF2a is a hormone that is naturally produced by the inner lining of the uterus of a non-pregnant mare at approximately 14 days after ovulation. It then binds to specific receptors expressed on the surface of cells that make up the corpus luteum (CL) and causes the cells to degenerate and to stop producing progesterone. It is important to note that the receptors for PGF2a are not expressed until 6 days post-ovulation. For this reason, prostaglandin is not effective unless it is administered at least 6 days after ovulation. Once the CL begins to regress, progesterone levels subside, then diestrus is interrupted and the mare usually returns to estrus within 72 hours after treatment.

    Commercial prostaglandin preparations that are often used for horses include Lutalyse (see page H495) and Estrumate and are available from a veterinarian. Practical uses for PGF    2a include "short-cycling" and termination of pregnancies. Short-cycling is a term used do describe a shortened diestrus phase. Inducing a shortened cycle is useful in the following ways:
    1. Controlling the timing of estrus to avoid competitions or events.
    2. Treating intrauterine infections.
    3. Controlling the timing of estrus for logistical reasons related to stallion or personnel availability.
       
    Sometimes with the use of PGF    2a, problems arise if the mare develops large follicles during diestrus. Normally these follicles will regress prior to the next estrus period, but PGF2a can sometimes cause them to ovulate and subsequently form a CL. Should this occur, the first CL will regress, but estrus will be prevented by the emergence of a CL from the second (induced) ovulation.

    A great deal of caution should be practiced when handling prostaglandin to protect the user from potentially serious health complications. Prostaglandin belongs to a class of chemicals that is readily absorbed through the skin and can cause a variety of problems including acute respiratory attacks in asthmatics and irregular menstrual activity and abortions in women.
     
  2. Progesterone is naturally produced by the CL during diestrus and has a quieting effect on the reproductive tract. Exogenous treatment with progesterone or another progestin is useful in prolonging the diestrus phase of the cycle. Non-pregnant mares can be maintained on progesterone, thereby avoiding estrus for at least 90 days with no detectable complications. However, it is very important that progesterone use is avoided in mares that may have an intrauterine infection. This is because the pathogenic organisms associated with a uterine infection are more able to proliferate in the mare’s uterus when it is under the influence of progesterone.

    Progesterone administration is often used to help maintain pregnancies that would otherwise be lost during periods of stress or illness. It may also help resolve luteal insufficiency during early pregnancy in some susceptible mares. Stemming from this practice, breeders will often use progesterone as a treatment for mares that have a history of abortion with the hope that the added progesterone will help ensure the health and continued development of the unborn foal. Breeders should be cautioned that unless the mare’s problem is inadequate progesterone production resulting from either luteal or placental insufficiency (these conditions are very rare), extra (exogenous) progesterone has not been shown to have any benefit toward maintaining viable pregnancies in mares that abort repeatedly.

    Due to a short shelf life, analogs have been developed which last longer and simulate the actions of natural progesterone. The analog used in horses, Altrenogest, is commercially available in the preparation, Regu-Mate (see page H703). Regumate is administered orally at a daily dosage rate of 1 mL for every 100 lbs. body weight. Like prostaglandin, progesterone is readily absorbed through the skin. While the effects of progesterone are less severe, menstrual irregularities in women can result, and pregnant women should avoid contact with progesterone or related preparations.
     
  3. Intrauterine Placement of Glass Marbles is a method of estrous cycle manipulation that has been used for a number of years in Europe and the Middle East and was introduced to the United States in 2001. It involves the placement of a sterile, 30 to 35 mm diameter glass marble through the cervix and into the uterus within 24 hours after ovulation. It is effective in increasing the interovulatory interval from 21 days to approximately 90 days in about 75% of mares. It seems to work by causing the uterus to react to the marble as if it were an embryo. Accordingly, the CL is then maintained for a substantially extended period. During estrus, the marble can be removed by a veterinarian who is experienced in transrectal uterine palpation. The veterinarian will manipulate the marble, per rectum, though the uterus and out through an open cervix. No adverse effects of this treatment have been reported.
     
  4. Human Chorionic Gonadotropin (hCG) is an LH-like hormone that is naturally produced by the developing human placenta and has the effect of maintaining the mother’s CL. In horses, this same hormone is commonly used during estrus to simulate an LH surge, thereby hastening ovulation. The typical dose ranges from 2000 to 3500 IU, and if administered when the developing follicle is greater than 35 mm in diameter, ovulation will normally occur within 48 hours. Often, when access to the stallion is limited, breeders will administer hCG on the day of breeding to help ensure that a repeat breeding will not be required 2 days later.

    A common problem arises when hCG is used more than once in a particular season. Since the makeup of hCG is human, not equine, the immune system of the horse recognizes it as a foreign substance and will make antibodies to inactivate it and remove it from the bloodstream. While repeated administration does not typically result in any ill effects, in many mares, hCG will cease to be effective.
     
  5. Gonadotropin Releasing Hormone (GnRH): Recently, another treatment has become available to induce ovulation without risk of causing the mare to become immunologically resistant to repeated administrations. Deslorelin acetate is a gonadotropin releasing hormone (GnRH) analog used in the form of a slow release implant available as Ovuplant. Naturally, GnRH acts on certain cells of the pituitary gland to cause the release of either LH or FSH depending on whether the mare is in estrus or diestrus. Released slowly, deslorelin acetate acts like the natural GnRH release that stimulates LH release and causes ovulation to occur. Treatment of mares with Ovuplant during estrus, after the development of a 30 mm follicle, will cause ovulation between 48 and 72 hours after the implant has been placed under the skin.

    A side effect of using this method is that it can delay return to estrus an additional 3-7 days from normal. However, this effect can often be prevented if the implant is removed when ovulation is detected.

Summary: In managing mares to improve their reproductive efficiency, breeders often find it useful to change or manipulate the normal progression of the estrous cycle in mares. Scientific research is ongoing to develop and produce reliable methods that modern breeders can use to manage mares more effectively.