CHAPTER 13Ovarian Abnormalities
Abnormalities of ovarian function are not uncommon in the mare. Ovarian problems may be due to a permanent developmental condition (i.e., chromosomal abnormality), transient physiologic condition (i.e., anovulatory follicle), or an acquired pathologic condition (i.e., ovarian tumor). Clinical techniques that may be used in the diagnosis and differentiation of ovarian abnormalities include behavioral observations, general physical examination of the mare, palpation of the ovary per rectum, ultrasonography of the ovary per rectum, hormone analysis, laparoscopy/laparotomy, ovarian biopsy, and karyotyping.
It is often helpful to develop a differential diagnosis list when presented with a mare that may have an ovarian problem. In most instances the list of potential diagnoses can be narrowed to one or two based on clinical observations and ultrasonographic examination. Measurement of ovarian hormone levels, chromosomal evaluation, and other more expensive and/or invasive diagnostic tests are only occasionally required to provide a diagnosis or confirm a presumptive diagnosis. A list of diagnoses for small/inactive ovaries and enlarged ovaries are presented in Box 13-1.
Box 13-1 Differential Diagnosis for Small/Inactive Ovaries and Enlarged Ovaries in the Mare
CHROMOSOMAL AND DEVELOPMENTAL ABNORMALITIES
Chromosomal abnormalities, especially of the sex chromosomes, have been associated with infertility in the horse (see Chapter 10). The prevalence of sex chromosome abnormalities in the mare has been reported to be less than 3%. A chromosomal abnormality may be suspected in a mare of breeding age with primary infertility and gonadal hypoplasia, especially if the mare is presented during the physiologic breeding season and has not been administered exogenous hormones.
The normal chromosome number of the domestic horse is 64, which consists of 62 autosomes and 2 sex chromosomes.1 The karyotype of the normal mare and stallion are 64,XX and 64,XY, respectively. Horses of all domestic breeds have the same number, size, and shape of chromosomes. The most commonly reported chromosomal abnormality of the horse is 63,X gonadal dysgenesis, in which only a single sex chromosome is present.2 The condition may occur when the sex chromosome pair fails to separate during meiosis, producing one gamete without a sex chromosome and another with two sex chromosomes. The equine condition is analogous to Turner’s syndrome in humans. The 63,X (or XO) condition has been detected in most domestic horse breeds, including draft and miniature breeds.
Horses with gonadal dysgenesis develop as phenotypic females because of the absence of a Y sex chromosome, or more specifically absence of the sex-determining region (Sry) normally present on the Y chromosome. Affected horses may be normal or small in size for their age and breed and have small ovaries with limited or no follicular development. The uterus and cervix are generally small and flaccid, and the endometrial glands are hypoplastic. The external genitalia are female, but the vulva may be smaller than normal and there is no clitoral hypertrophy. XO mares may exhibit anestrus or irregular estrous behavior and occasionally stand to be mated. True XO mares are considered to be sterile. However, mares with a mosaic or chimeric karyotype (i.e., 63,XO/64,XX) are not always small in stature, and some have been reported to produce a foal. Mosaic mares account for approximately 15% to 30% of all cases of gonadal dysgenesis. Numerous other chromosomal abnormalities have been reported in the mare in addition to XO gonadal dysgenesis.3
Occasionally a horse that has a developmental abnormality of the reproductive tract may present for evaluation. Although true equine hermaphrodites have been reported,4 the most common developmental abnormality of the reproductive tract is male pseudohermaphroditism (XY sex reversal syndrome).5 Affected horses are phenotypic mares or masculinized intersex horses with a male karyotype (64, XY) and cryptorchid testes. Sex phenotype and behavioral traits (i.e., expression of aggressive or stallion-like behavior) are correlated with blood testosterone levels.6 The point to be made is that not every mare exhibiting male behavior has a granulosa-theca cell ovarian tumor. Other possibilities should be on a differential diagnosis list, including pregnancy, exposure to anabolic steroids, and intersex conditions.
Diagnosis of a chromosomal or developmental abnormality may be based, in part, on chromosome analysis or karyotyping. Karyotyping can be performed on any tissue with actively dividing cells. A fresh blood sample collected into acid citrate dextrose or heparin may be sent by overnight courier to a laboratory specializing in animal karyotyping. Measurement of blood testosterone levels may be beneficial in the detection of cryptorchid testes in some phenotypic mares with XY sex reversal. Transrectal ultrasonography and/or laparoscopic evaluation of the abdominal cavity may also be used to locate and evaluate gonads and internal genitalia. Histologic evaluation of biopsied or excised gonadal tissue may be necessary to confirm a diagnosis of true hermaphroditism.
Due to the etiology of the conditions, no treatments are possible to correct chromosomal or developmental abnormalities of the reproductive tract. Castration is recommended for male pseudohermaphrodite horses.
AGE-RELATED OVARIAN DYSFUNCTION
Geriatric mares may have reduced reproductive performance due to age-related changes in ovarian function, uterine health, perineal conformation, and other factors.7 Older mares may experience a delay in their initial ovulation of the year by an average of 2 weeks. Geriatric mares may have a longer interovulatory interval than younger mares because of a longer follicular phase.8,9 A lengthening of the follicular phase in association with elevated gonadotropin concentrations may indicate impending reproductive senescence in older mares.10 Aged mares may also have decreased oocyte viability and a higher incidence of early embryonic loss and abortion. Complete ovulation failure or ovarian senescence has been observed in aged mares and may be due to an insufficient number of primordial follicles. The incidence of pituitary adenoma (pituitary pars intermedia dysfunction, also known as Cushing’s disease) is also increased in older mares and may contribute to poor reproductive performance.
No effective treatments are currently available in the mare for promoting follicular growth in senescent ovaries.
EXOGENOUS HORMONE TREATMENT
Anabolic steroid administration may affect estrous behavior and ovarian function. Treatment of mares with low doses of anabolic steroids may cause aggressive or stallion-like behavior, whereas high doses may inhibit ovarian activity and result in failure of follicular development and ovulation.11 Anabolic steroids may also suppress pituitary gonadotropin secretion.12 Administration of anabolic steroids to prepubertal fillies may result in clitoral hypertrophy. The use of anabolic steroids should be avoided in fillies and mares intended to be used for breeding.
Progestins are commonly given to cycling mares for the suppression of estrus or synchronization of ovulation.13 Mares may continue to ovulate during progestin administration, especially if treatment is started late in the luteal phase. A high incidence of persistent corpus luteum formation has been noted for mares ovulating during progestin treatment.14
Deslorelin acetate is a potent gonadotropin-releasing hormone (GnRH) agonist used to induce a timed ovulation in mares. The commercial product (Ovuplant) is a biocompatible implant designed for subcutaneous administration. The GnRH agonist stimulates release of luteinizing hormone (LH) from the anterior pituitary, which induces follicular maturation and ovulation. After the implant was used extensively in the United States in 1999 and 2000, reports suggested that some individual mares treated to induce ovulation that did not become pregnant may have experienced a delayed return to estrus and a prolonged interovulatory interval.15 Subsequent studies determined that use of the implant may be associated with prolonged suppression (down-regulation) of follicle-stimulating hormone (FSH) secretion from the pituitary, a decrease in follicular development in the diestrous period following the induced ovulation, and a lengthened interovulatory interval.16,17 Administration of prostaglandins 7 to 8 days after ovulation to induce luteolysis, as routinely provided after an embryo collection attempt, increases the risk of delayed follicular development. Removal of the deslorelin implant 48 hours after administration has been reported to prevent the adverse effects on pituitary function and does not alter ovulation rates.18 For ease of removal, the implant may be inserted subcutaneously by using the implant device provided by the manufacturer in a region of the vulva that has been infused with a small amount of local anesthetic.19 After ovulation, the implant may be removed through the original tract created by the implant device by using gentle topical pressure.
EQUINE CUSHING’S DISEASE
Mares with hypertrophy, hyperplasia, or adenoma formation in the pars intermedia of the pituitary (equine Cushing’s disease [ECD]) have been reported to have a variety of medical and reproductive problems. Reproductive abnormalities reported in mares with ECD have included abnormal estrous activity,20 estrous suppression,21 and reduced fertility.22 Potential cause(s) of the reproductive abnormalities in mares with ECD may be destruction of the gonadotrophs of the anterior pituitary due to compression by the enlarged pars intermedia23