Jon Palmer, VMD, Associate Professor, New Bolton Center, University of Pennsylvania
Fescue grass is a very common forage found in many parts of the United States. It is commonly part of lawn and cover grass mixes since it has the desirable qualities of being hearty and drought resistant. This grass is not toxic by itself, however when infected by an endophytic fungus ingestion results in a toxic reaction to herbivores. The fungus involved is Acremonium coenophialum. In cattle, the toxicosis results in lower weight gains, increased body temperature, rough hair coat, gangrenous necrosis of tissue in feet, tails and ears, and reduced conception rates. In horses however the only toxic reaction appears to be associated with reproductive abnormalities in gravid mares.
Mares consuming endophyte infested tall fescue have prolonged gestation lengths, weak or stillborn foals, retained placenta, thick placental tissue, mild to severe dystocia, rebreeding difficulties, and agalactia. Gestation duration may increase from the normal 334 days to 360 days or more. Foal fetuses fail to rotate into proper position for delivery contributing to dystocia. Over 50% of mares will retain their placenta. The mares have decreased serum progesterone and prolactin concentrations resulting in poor udder development and agalactia in up to 90% of mares.
Foal's born after the prolonged gestation appear dysmature with large skeletal frames and muscle wasting. The large skeletal frames contribute to the dystocia. Foals are often born with signs of hypoxia/asphyxia. Up to 50% of the foals die.
One of the principle ergot alkaloids produced by A. coenophialum, ergovaline, acts as a dopamine agonist at the DA2 dopamine receptors in the pituitary, suppressing prolactin and ACTH secretion. Selective DA2 dopamine receptor antagonists such as domperidone and sulpiride effectively prevent the inhibitory affects of ergovaline on prolactin and ACTH release. Induction of hormonal events leading to parturition are under fetal control. Progesterone concentration increases and estrogen concentration decreases during the last 30 days of gestation. Both of these changes do not occur in mares grazing endophyte infested tall fescue. There is some evidence that the rise in progesterone is associated with increase in cortisol levels in the fetuses and placental transformation of these into progesterones. Since dopamine and ergot alkaloids may inhibit ACTH secretion by binding with DA2 receptors in the pituitary, they may effectively block this rise in fetal cortisol. At least in sheep, ergot alkaloids pass through the placental and affect fetal pituitary secretions. A similar mechanism may occur in foals, and the prolonged gestation seen with grazing infested fescue may be the result of ergovaline's activity on the fetal pituitary.
Pergolide and bromocriptine are dopamine agonists used in the treatment of pituitary adenoma/hyperplasia in horses. Pergolide is an oral, semisynthetic ergot alkaloid derivative used in the management of Parkinson's disease in man. Pergolide directly stimulates postsynaptic dopamine receptors and is one of the most potent dopaminergic agonists. Pergolide stimulates both DA1 and DA2 receptors. Bromocriptine is a synthetic dopamine agonist that is chemically related to ergot alkaloids. Bromocriptine stimulates DA2 receptors and antagonizes DA1 receptors in the hypothalamus and the neostriatum of the CNS. Both of these drugs appear to delay parturition and cause agalactia resulting in clinical signs similar to fescue toxicosis.
The most important step in treatment is removing mares from fescue pastures at least 30 days before their due date. Although the affect of the toxin has not been well defined earlier in pregnancy, if it is removed from the diet within thirty days of foaling, it appears that the effects are completely reversible. The dopamine antagonist domperidone, is commonly used to treat fescue exposed mares. This drug is usually given at the dose of 1.1 mg/kg once a day. Studies have shown that mares who remain on infested fescue but receive domperidone for the last 25 days of gestation will have normal gestation lengths, no dystocia and the live foals. They also will have normal lactation and normal levels of immunoglobulin in their colostrum. Domperidone has also been used for agalactia caused by other reasons. It's efficacy in such cases is unproven.
Prevention is based on keeping pregnant mares off of fescue pastures. Although all fescue pastures are not infected by the endophyte, many are. Historically the endophyte was confined to certain areas, especially in the south. However the endophyte has spread and many of the previously identified free pastures are infested. The range of the diseased now appears to be throughout most of North America. New fescue mixes have been developed which are endophyte free, however they may eventually become infected. Most horses will avoid grazing on fescue unless there is little else to eat. Since fescue his drought resistant, in dry years there may be little else to graze resulting in increased fescue consumption. The percentage of fescue in the diet appears to be less important than the absolute amount. Recognition of this problem and the availability of domperidone should result in the elimination of this toxicosis, despite the fact that over 500,000 horses are kept on tall fescue pastures.