Ergot Alkaloid (ergopeptine)
Toxicity in Horse Hay and Pasture
Table of Contents
- Fescue Toxicity
- Ergot Alkaloid Toxicity in the Late-gestation
- Sampling and Analysis
- The Ontario Situation
- Prevention and Recommendations
- Related Link
Losses of foals, at birth and early gestation, remind us that pregnant
mares are very susceptible to a number of bacterial, viral and nutritional
challenges. In 2001, a number of practitioners in Kentucky and Ohio
reported two separate syndromes;
- agalactia (little or no milk), difficult extended foaling, "red
bag" placentas (premature separation of the placenta), edematous
placentas, weak or dead foals with aspiration pneumonia; and
- mares diagnosed pregnant by ultrasound at 45 days post breeding
were found with a dead fetus by day 60.
The first syndrome resembles fescue toxicity except that, in these
cases, the gestation period was normal. The second syndrome has
not been described in association with the mycotoxins of endophyte-infected
fescue. Fescue, as well as most hay and grain crops, can be colonized
by fungi which produce an array of mycotoxins. The ergot alkaloids
and the fusarium mycotoxins are the main mycotoxin groups of concern.
For this review, we will use the more general term ergot alkaloid(s)
to also include the ergopeptine alkaloids. Colonization of both
grain and hay crops and the tendency to produce mycotoxins by fungi
is dependant on environmental conditions. The clinical conditions
caused by these fungi are not well described for horses. The sequence
of events leading to the natural occurrence of the fungi and their
mycotoxins is often unknown.
Two types of colonization can occur. The endophytes live between
the plant's cell walls and include the more common genera Balansia,
Epichloe, Acremonium and Neotyphodium. The non endophytic fungi
do not live intercellular and include the more common genera Claviceps,
Stachybotrys, Fusarium and Penicillium. The endophytes, and Neotyphodium
specifically, complete their entire life cycle within the plant.
The spread of the endophyte from one generation of plant to another
is by way of the seed. The non endophytic fungi generally have a
sexual cycle outside of the plant. Claviceps, specifically, has
a life cycle which consists of: an airborne ascospore infecting
the inflorescences (flower) of the plant; followed by the formation
of the honeydew and sclerotia which replace the ovary; sclerotia,
which are masses of mycelium, mature and fall to the ground forming
stalked stromata which in turn produce ascospores (1).
In many ways these fungi are very similar, since sometimes they
may be asexual and sometimes have a sexual cycle. This discussion
will be limited to the genera of fungi, Neotyphodium and Claviceps.
Most of the fungi in these two genera produce a similar array of
ergot alkaloids. The fusarium mycotoxins will be discussed in another
fact sheet since they are normally associated with concerns when
harvesting wheat or corn. However, when investigating clinical problems,
remember to analyse for the fusarium mycotoxins. Background levels
of the fusarium mycotoxins are commonly found in hay and pasture
Neotyphodium coenophialum was formerly called Acremonium coenophialum.
The endophytic fungus produces mycotoxins, resulting in the disease
condition called fescue toxicity. The mycotoxins of endophyte-infected
fescue belong to the class of chemicals called ergot or more specifically
ergopeptine alkaloids. They are well recognized as causing dystocia
in mares and deaths of foals in the United States. The primary clinical
signs of ergot alkaloid poisoning in the late-gestation mare include:
- an extended gestation length from 11 to 12 months,
- dystocia, with mares sometimes trying to foal for many hours,
- agalactia (little or no milk) with poor quality colostrum (low
- "red bag" placentas from premature separation
- thick edematous placentas with weights exceeding 6.5 kg for
a thoroughbred mare,
- weak or dead foals with aspiration pneumonia from struggling
to get out through a thickened placenta.
No studies have shown the effect of ergot alkaloids in horses other
than with late-gestation mares. Fescue is grown extensively in the
arid areas of the USA because of its ability to withstand drought
and its resistance to many insect infestations. Fescue is not commonly
grown for pasture or hay production in Ontario. Endophyte-free varieties
have been developed to get away from the problems caused by these
mycotoxins. Endophyte-infected varieties of fescues are commonly
used for erosion control and golf greens. Occasionally, endophyte-infected
seed will be accidentally sold to horse owners.
Neotyphodium lives in a symbiotic relationship with the plant,
gaining nutrients to live on while providing chemical protection
against grazers, both insect and higher life forms and some resistance
to drought. Neotyphodium completes its entire life cycle within
the plant. It passes from one generation of the grass to the next
in the seeds of the plant. The main alkaloid produced by Neotyphodium
is ergovaline. However, many other ergot alkaloids can be found.
Ergotism is the clinical syndrome caused by the genera, Claviceps.
It is a non endophytic fungus which lives on the plant, utilizing
the plant's nutrients without a recognizable benefit to the host.
Claviceps can live on a variety of hays and pasture grasses and
produce fruiting bodies on bluegrass and cereal rye. Ergotism is
probably the oldest known mycotoxicosis. The ergot alkaloids of
Claviceps purpurea are hallucinogenic. Consumption of infected rye
bread has been associated with human outbreaks which date back some
2,000 years. Claviceps has a sexual life cycle as previously described
with the ovary of the plant being replaced with a whitish mycelial
mass which enlarges, darkens and eventually hardens into a sclerotium
or fruiting body. The Claviceps sclerotia contain a large array
of chemicals. Many of these same chemicals are also commonly found
in the endophytic infected grasses (1). Different genera of fungi
produce the ergot alkaloids in different proportions. Claviceps
commonly produces ergotamine, ergostine, ergocristine, ergocryptine
and ergocornine (2).
Two clinical cases involving the production of ergot alkaloids
by Claviceps have been associated with fetal loss in late-gestation
mares. The first case is from Brazil (3). Late-gestation mares,
which were fed oats containing ryegrass seed, suffered fetal losses
similar to the clinical condition of fescue toxicity. The authors
indicate that the ryegrass seed was the only source of ergot alkaloids.
The second case is an investigation in which cereal rye straw bedding
was being consumed by late-gestation mares (4). The clinical syndrome
was similar to fescue toxicity except that the mares foaled around
their normal due date. Of the first 8 mares to foal, 7 had dead
foals. High-performance liquid chromatography (HPLC) analysis of
the bedding indicated the presence of two ergot alkaloids, each
equivalent to 450 ppb. One was identified as ergocornine. A second
laboratory tested the straw bedding and found a large peak just
ahead of 2.2 minutes retention time. This peak was adjacent to the
Ergot Alkaloid Toxicity in the Late-gestation
Mares are sensitive to ergopeptine alkaloids at levels as low as
50-100 ppb., while cattle do not show visible signs until 1000-2000
ppb. These alkaloids exert toxic effects on the reproductive tract
and mammary gland of the mare and have been associated with depression
of serum prolactin and progestagens (5 alpha-pregnanes), a prolonged
gestation, a thickened edematous placenta and agalactia (5). The
ergopeptine alkaloids interfere with the normal rise of progestagens
(mainly 5 alpha-pregnanes) and prolactin in the last 40 days of
gestation. The progestagen levels normally increase from 300 days
to birth (4.8 + 1.5 to 22.7 + 2.7 ng/ml.). Suppression of progestagen
levels indicates ergopeptine toxicity (5). Dr. Brendemuehl, Oregon
State University, uses a commercially available radioimmune assay
(RIA) progesterone assay to measure total immunoreactive progestagens
in pre-foaling sera of mares.
Foals born without the normal increases in maternal progestagens
suffer hypoadrenocortical function and are small, weak or stillborn
(5). Edema of the placenta increases the placental weight. The placental
weight of the normal thoroughbred mare is reported as 5.7 + 0.08
kg. or about 12.5 lbs. or 11% of the foals body weight (6, 7).
Sampling and Analysis
When placental edema is diagnosed, the attending veterinarian will
need to determine if it is caused by an ergot alkaloid. Samples
of possible sources of ergot alkaloids including feed, grain and
hay will all have to be tested. Laboratory testing for ergovaline
(the ergot alkaloid of fescue toxicity) and lolitrem B (the ergot
alkaloid of perennial rye grass) are commonly available. Dr. Morrie
Craig's laboratory, Oregon State University, analyses thousand of
samples annually for ergovaline. It is difficult to analyze for
other ergopeptine alkaloids due to the lack of control standards.
Mares in the last 30 days of pregnancy can be monitored for placental
edema by ultrasound. Low pre-foaling progestagen levels in the late-gestation
mare are indicative of exposure to ergot alkaloids. Monitoring of
progestagen levels is done by collecting serum samples from the
mares when they enter the foaling barn (approximately 330 days gestation).
A comparison with a second serum sample around day 335 of gestation
would show whether there is a normal rise or peaking in progestagen
level. Levels below 15 ng/ml. are suspicious of ergot alkaloid toxicity.
A pre-foaling serum progestagen level below 5 ng/ml. is seen with
fescue toxicity. In 50% of normal mares, progestagen levels drop
6-10 hours prior to foaling.
The Ontario Situation
During the 1999 foaling season, an investigation found that cereal
rye straw bedding containing ergot alkaloids was responsible for
thickened edematous placentas, agalactia and seven perinatal deaths
in foals. In the 2000 foaling season, four Ontario farms experienced
edematous placentas. One placenta weighed 14 kg. One of the farms
observed that 49% of the placentas from 78 mares weighed 6 kilograms
or greater. The attending veterinarian observed edema in 18% of
the 78 placentas (8). A definitive cause of the edema was not determined
in these cases. Preliminary analysis of the non-fescue hay revealed
the sporadic presence of an ergopeptine alkaloid(s) which could
not be identified. It is hypothesized that the sporadic occurrence
of placental edema in foaling mares results from the presence of
an ergot alkaloid(s) less pharmacologically active than ergovaline
in non-fescue hays in Ontario.
Prevention & Recommendations
- Mow grass pastures to keep them in a vegetative state rather
than letting them develop seed heads. This will minimize the opportunity
for airborne ascospore from invading pasture plants.
- Never feed sclerotia-containing grain to late-gestation mares.
- Never allow late-gestation mares to eat cereal rye straw bedding
- Ensure that all pasture/hay seed mixes containing tall fescue
and perennial rye grass are guaranteed endophyte free. A sample
of the seed can be sent to a laboratory for testing prior to seeding.
- Samples of hay and pasture can be tested for the presence of
ergovaline and lolitrem B. The testing for other ergot alkaloids
is dependant on the laboratory having adequate control standards
to compare to.
- Choose a laboratory which uses HPLC methodology. Thin layer
chromatography (TLC) is not sensitive enough to identify ergot
alkaloid levels less than 1 ppm. Pregnant mares are known to have
foaling problems at half of this level.
- Use a foaling record form and examine each placenta as suggested
in the information sheet, Examining the Mare's Placenta and
Keeping Foaling Records (9). Pay particular attention to
placenta weights. Placenta weights greater than 11% of the foal's
weight are of concern. For thoroughbreds, the placenta weight
should not exceed 6.5 kg.
- Submit all heavy placentas and dead newborn foals to the laboratory
- If placenta weights are high, collect pre-foaling sera from
late-gestation mares and determine the progestagen (5 - alpha
pregnane) level and/or ultrasound the late-gestation mares for
- Mares can be treated with domperidone should an ergot alkaloid
problem be suspected.
- Bacon CW. Fungal endophytes, other fungi, and their metabolites
as extrinsic factors of grass quality. In: Forage Quality, Evaluation
and Utilization. Nutrition Conference on Forage Quality, University
of Nebraska, 1994: 318-366.
- Lacey J. Natural occurrence of mycotoxins in growing and
conserved forage crops. In: Mycotoxins and Animal Foods. CRC
Press, Inc., Florida, 1991: 363-397.
- Riet-Correa F, Mendez MC, Bergamo PN, Flores WN. Agalactia,
reproductive problems and neonatal mortality in horses associated
with the ingestion of Claviceps purpurea. Australian Vet. J.
1988 ; Vol 65, 6:192-193.
- Wright RG, Boyce B, Van Dreumel T, Hazlett MJ, Cross DL.
Ergot alkaloid toxicity in foaling mares associated with eating
cereal rye straw. Abstract presented at Equine Nutrition and
Physiology Symposium, Lexington KY May 28/01.
- Brendemuehl JP, Williams MA, Boosinger TR, Ruffin DC. Plasma
progestagen, tri-iodothyronine, and cortisol concentrations
in postdate gestation foals exposed in utero to the tall fescue
endophyte Acremonium coenophialum. In: Equine Reproduction VI.
Biology Reprod Mono 1, 1995: 53-59.
- Whitwell KE , Jeffcott LB. Morphological studies on the fetal
membranes of the normal singleton foal at term. Res. Vet. Sc.
- Schlafer DH. Gross examination of equine fetal membranes:
What's important - What's not! Proceedings of the Equine Symposium:
Society for Theriogenology/ American College of Theriogenologists,
San Antonio, Texas 2000.
- McEwen B, vanDreumal T, Wright RG. Equine abortion update.
AHL Newsletter, 2000:4 (2): 24.
- Wright RG, Kenney D. Examining the mare's placenta and keeping
foaling records. Ontario Ministry of Agriculture, Food and Rural
Affairs, Guelph, Ont. April 2001.
the Mare's Placenta and Keeping Foaling Records