Current aspects of reproductive endocrinology in the mare

Discussion

The use of exogenous reproductive hormones and/or hormone analogs is a mainstay of clinical practice in equine reproduction. With the exception of equine follicle stimulating hormone (eFSH) all of the major hormones secreted by the hypothalamic-pituitary- ovarian axis are available as exogenous formulations that are used to regulate physiological and/or behavioural reproductive phenomena in mares. Although native gonadotropin releasing hormone (GnRH) is commercially available in aqueous injectable formulations their short circulating half-life limits the usefulness of these products in mares; therefore, potent GnRH analogs such as deslorelin are used, generally to induce ovulation in mares that are in oestrus with a growing dominant follicle (>30 mm). Administration of deslorelin stimulates the release of luteinising hormone (LH) from the anterior pituitary gland, which initiates follicular/oocyte maturation and ovulation approximately 36 - 48 h after administration.
Human chorionic gonadotropin (hCG) is used to induce ovulation in mares because of its LH-like activity. Like deslorelin, hCG is typically administered to mares that are in oestrus with a growing dominant follicle (<35 mm). The LH-activity of the hCG induces follicular/oocyte maturation resulting in ovulation approximately 36 - 48 h after treatment. For mares in which hCG has not reliably induced ovulation, or there is concern the response will be variable (e.g. aged mares), the use of deslorelin is generally warranted. Although FSH products are used extensively for superovulation prior to embryo transfer in cattle and other livestock species, the FSH products that are used are of porcine origin and are not efficacious for superovulating mares. An equine FSH (eFSH) preparation had been commercially available for superovulating mares; however, that product was subsequently withdrawn from the market. A recombinant equine FSH (reFSH) product is currently being evaluated for superovulating mares, but it is not commercially available at this time (Meyers-Brown et al. 2010).
Exogenous formulations of the ovarian steroid hormones oestrogen and progesterone are used extensively, alone and in combination, to regulate and/or treat numerous physiological and pathological conditions in mares (Pinto 2011; Tibary 2011). Oestrogen is administered to ovariectomised mares to induce oestrous behaviour for breeding shed activities; to spring 'transitional' mares prior to administration of dopamine antagonists such as sulpiride to hasten the onset of ovulation; and to noncycling (or ovariectomised) oocyte or embryo recipient mares to enhance the responsiveness of the uterus to subsequent progesterone treatment. Progesterone and the synthetic progestin altrenogest are widely used for reproductive management in both nonpregnant and pregnant mares. They are used to suppress oestrous behaviour in nonpregnant performance horses and in spring 'transitional' mares to hasten the onset of ovulatory activity. In pregnant mares exogenous progestins are used extensively (whether warranted or not) to augment endogenous progesterone levels in an effort to enhance maintain pregnancy during early gestation (<100 days). Exogenous progestins are also used for maintenance of pregnancy in nonovulating (or ovariectomised) oocyte or embryo recipient mares that lack an endogenous source of progesterone (until fetal-placental production begins) and as an adjunctive therapy in high-risk pregnant mares, such as those with placentitis or severe systemic disease. Progesterone in combination with oestrogen is routinely used for synchronising oestrus/ovulation in cycling mares and it can be used in post partum mares to delay estrus/ovulation in an effort to enhance the fertility of foal-heat breeding.
Prostaglandin F2alpha (PGF2alpha) has applications in nonpregnant
and pregnant mares (Staempfli 2011). Two formulations of PGF2alpha are available, native PGF2alpha (dinoprost tromethamine) or the synthetic analog cloprostenol. The most common use of PGF2alpha in nonpregnant mares is to induce luteolysis and bring mares into heat. Although administration of 2 doses of PGF2alpha 14 days apart has been used to synchronise oestrus/ovulation, it is not a reliable way of achieving that goal in mares, so more efficacious methods of oestrus/ovulation synchronisation are used (e.g. treatment with progesterone and estradiol-17beta), which incorporate a single PGF2alpha treatment to eliminate endogenous progesterone secretion from a corpus luteum (CL). Prostaglandin F2alpha is also used in nonpregnant mares for its ecbolic effect to stimulate uterine contractile activity for the treatment of uterine fluid accumulation associated with persistent mating-induced endometritis. Exogenous PGF2alpha will stimulate uterine contractile activity for a duration of 4 - 5 h, with cloprostenol inducing a more consistent response than native PGF2alpha, so it is the agent of choice for this application. It is important to note, that although historically the CL has been considered to be resistant to the luteolytic effects of PGF2alpha until Day 5 after ovulation, it has been demonstrated that CL function is altered following administration of PGF2alpha as early as Day 2 after ovulation. Therefore, when using exogenous PGF2alpha to treat mares for fluid accumulation during oestrus, treatment should not be continued beyond the day of ovulation. Administration of PGF2alpha is the preferred method of terminating pregnancy during early gestation in mares. Prior to approximately 30 - 35 days of gestation, administration of a single dose of PGF2alpha is reliably abortifacient through its luteolytic effect causing endogenous progesterone levels to fall below the threshold necessary for continued maintenance of pregnancy. After 35 days of gestation, coincident with formation of the endometrial cups and secretion of equine chorionic gonadotropin (eCG) that induces supplemental CL formation, multiple PGF2alpha treatments may be necessary to induce abortion. After fetal- placental production of progesterone/progestins becomes sufficient to maintain pregnancy without an ovarian/luteal source of progesterone (>100 days of gestation), PGF2alpha can still be used to induce abortion in mares, however multiple treatments will be required over the course of several days.
The use of exogenous oxytocin has applications in nonpregnant, pregnant and post partum mares (LeBlanc 2011). In nonpregnant mares oxytocin has revolutionised the clinical management of endometritis, both persistent mating-induced endometritis and infectious endometritis, because of its ability to stimulate uterine contractile activity and enhance clearance of intraluminal fluid. Depending upon the clinical circumstances, oxytocin can be used alone or it can be combined with large volume uterine lavage. Oxytocin stimulates uterine contractile activity for approximately 30 - 45 min, so repetitive doses are often given during the day in an effort to maximise uterine clearance. A newly described use of exogenous oxytocin in nonpregnant mares is administration during diestrus to disrupt luteolysis to prolong CL function as a means of oestrus suppression in performance mares (Vanderwall et al. 2012). The primary use of oxytocin in pregnant mares is for induction of parturition and numerous protocols for this purpose have been described (LeBlanc 2011). In post partum mares oxytocin is routinely used as an aid in the treatment of retained fetal membranes. Treatment is generally initiated if the fetal membranes have not been passed within 3 h after parturition, and typically consists of administration of 5 - 20 units of oxytocin given i.v. or i.m., which may be repeated every 30 min to 4 h or alternatively given as a slow i.v. drip diluted in physiological saline. For refractory cases, administration of one liter of lactated Ringer's solution containing 100 - 150 ml of 23% calcium gluconate followed by 20 units of oxytocin i.v. is often successful (LeBlanc 2011).