Infertility in the mare.

Abstract

A nomalous sex chromosome comAposition is a cause of infertility in mares (1, 2, 3, 4, 5, 6, 7). Mosaicism is the occurrence of two or more genetically different cell types within the body of an individual (5). The impact of sex chromosome mosaicism on the fertility of an animal depends on the relative proportions of the two cell lines in the ovary. The mare may exhibit a Turner-like syndrome, which is an infertile condition characterized by streaked gonads, short stature, and cells containing only one X chromosome, or they may be only subfertile (1, 3, 5). The most severely affected mares have small, firm ovaries with undifferentiated ovarian stroma (3, 5). In such mares on rectal palpation, the uterus and cervix are generally small and flaccid. The external genitalia are female but the vulva is smaller than normal; there is no clitoral enlargement. Some affected mares have been reported to be smaller in height and weight than normal mares of their corresponding breeds. The response of affected mares to teasing by a stallion ranges from total rejection to allowing the stallion to mount and mate (4). Generally there is no cyclical pattern to the estrous behavior (4, 5). Affected mares are unresponsive to hormonal stimulation (6). During the 1986 breeding season, a four-year-old Standardbred maiden mare was presented with a history of persistent anestrus. The mare was 15 hands (152.4 cm) high and weighed approximately 400 kg. The mare was in good body condition with no other abnormalities noted. The mare was repeatedly examined by rectal palpation. The ovaries were 2.5 cm long and on one occasion a small 10 mm follicle was palpated. The uterus and cervix were small and persistently flaccid. A tentative diagnosis of Turnerlike syndrome was made. One intramuscular injection of 5 mg of dinoprost tromethamine (Lutalyse, Tuco Products Co., Orangeville, Ontario) was ineffective in inducing estrus. On May 2, 1986 a venous blood sample was taken and air-dried smears were stained with Wright's stain. On May 21, 1986 a heparinized blood sample was drawn from the jugular vein and taken to the Ontario Veterinary College (OW) for karyotyping. The blood smears were examined for the presence of "drumsticks" (a drumstick is a sex chromatin body or Barr body that appears as an appendage on a lobe of the nucleus in polymorphonuclear leukocytes in female mammals (5)). Two percent of the neutrophils (2 of 100) had drumsticks. The cultures of the heparinized blood sample were processed and subjected to karyotypic analysis. Of the twentysix cells examined, twenty-three (88.5%) were 64,XX and three were 63,XO. The normal chromosomal complement for the domestic horse, Equus caballus, is 2n = 64. Abnormal female karyotypes that impair fertility include the 63,XO aneuploid Turner-like syndrome, and mosaicism with 63,XO/ 64,XX cells (1, 2, 3, 4, 5, 6). The condition of the 63,XO gonadal dysgenesis may account for some cases of primary infertility in the mare (7). These two conditions are more common in the horse than in other domestic species. Possible reasons for this may be that mares are bred later in life and under artificially manipulated conditions (5). However, seasonal or age of conception patterns have not been established to date for the Turnerlike syndrome in mares. The cause of the chromosomal abnormality in this mare could be anaphase lag or nondisjunction at any time after fertilization (3, 4). The stage at which either of these mitotic accidents may have occurred affects the proportion of cells with the XO chromosomal composition (3, 4). If the germ cells were among the progeny of the abnormal cells the animal would be infertile or subfertile (1, 3). In humans with Turner's syndrome (45,XO) the fetal gonad is normal but all the germ cells perish at birth or soon thereafter (1). It is believed that both X chromosomes are required for oocyte survival. A mosaic 63,XO/ 64,XX mare could have ovarian development similar to that of a 63,XO mare or more normal development depending on the relative proportions of the two cell lines of the gonad (1). Estrogen deficiency due to gonadal insufficiency is found in affected mares. There is a low level of plasma estrogen and an elevated level of luteinizing hormone in the plasma and urine (4, 7). The flaccid cervix and uterus and the absence of cyclical estrus behavior are indicative of the estrogen deficiency in these mares (4). However, the levels of plasma luteinizing hormone and estrogen were not tested in the mare described herein. The 63,XO/64,XX mares may exhibit drumsticks on 1.75% of their neutrophils versus 8-12% in normal mares (4). The mare in this case had drumsticks on 2% of her neutrophils. Male horses and aneuploid 63,XO mares do not have drumsticks. This test is useful in reaching a tentative diagnosis only and should be confirmed by a karyotype (3, 4, 6). The examination of chromosomes was very useful in reaching a diagnosis in this case. Both skin and heparinized blood can be used for karyotypic culturing (1, 3). Although only 11.5% of the peripheral leukocytes were 63,XO it is possible that the germinal cell line had a higher proportion of63,XO cells. We were unable to determine this and the owner did not wish to have any more tests done