Poison Hemlock

Poison hemlock is most likely to be ingested in the spring, because it often is one of the first green forages to appear. Ingestion of poison hemlock (Conium maculatum) by pregnant cows during the gestation interval of days 50 to 75 induces multiple congenital contractures (MCCs) in calves, a condition commonly referred to as “crooked calf disease.”² Pregnant cows gavaged with the fresh green plant during days 50 to 75 of gestation had calves with arthrogryposis and spinal curvature, defects similar to those induced by administration of the isolated teratogenic principle coniine. Dams gavaged with the dry plant had either normal or equivocally deformed offspring, whereas those fed 410 to 840 g of fresh green plant daily from day 50 to 75 of gestation either aborted or delivered calves with limb deformities. Periodic ultrasound scanning during the treatment period revealed severe inhibition of fetal movement in goats.³ Suppression of fetal movement during the critical gestational window is thought to be the cause of the plant-induced cleft palate (suppression of tongue thrusting) and skeletal contractures. A similar mechanism is likely in cattle.

Lupines

Certain species of the Lupinus genera cause MCCs in calves exposed in utero during days 40 to 70 of gestation.⁴ Certain Lupinus species, such as Lupinus sericeus or Lupinus caudatus, contain anagyrine as the principal alkaloid and are teratogenic in cattle, but not in sheep and goats. The teratogen in Lupinus formosus is thought to be ammodendrine.⁵ This plant species has induced severe limb and spinal deformities together with cleft palate in calves. These defects were induced in calves when dams were dosed with 2.33 to 3.16 g of fresh plant/kg of body weight twice daily during days 40 to 70 of gestation. More recent data from epidemiologic studies suggest that the gestational period of teratogenic susceptibility may extend to day 100.⁶ The MCCs are similar to those induced by Conium and Nicotiana genera and include arthrogryposis, torticollis, kyphosis, scoliosis, rib cage deformities, and extension or flexure of the carpal or tarsal joints.

Tobacco

Nicotiana glauca (tree tobacco) is a small tree commonly found at lower elevations of California and Arizona. Seven cows dosed with dried, ground N. glauca daily from the 50th to 75th day of gestation produced seven calves with arthrogryposis of the forelimbs and curvature of the spine.⁷ Other abnormalities included general malpositioning and misalignment of the distal ends of the radius and ulna and the proximal ends of the metacarpal bones. Carpal joints were severely affected, fetlock and pastern joints less so, with lateral rotation of forelimbs common. One of four calves had moderate torticollis and scoliosis. Anabasine, not nicotine, is thought to be the teratogen. Nicotiana tabacum (common tobacco) is a known teratogen in swine,⁸ but such effects have not been documented in cattle.

Locoweeds

From an economic standpoint, the locoweeds—certain Astragalus and Oxytropis species—have more of an adverse impact on bovine reproduction than any other group of poisonous plants. Of the almost 400 species of Astragalus and 22 of Oxytropis, fewer than 20 have been verified to cause true locoism and the associated reproductive dysfunction. Undoubtedly, many more species will be found to contain swainsonine, the active toxic principle in locoweed. The multiple reproductive problems induced by chronic locoweed consumption include abortion, teratogenesis, fetal death, delayed placentation, deficient uterine and placental vascular development, hydrops amnii, hydrops allantois, abnormal cotyledonary development, decreased conception rate, reduced libido, and diminished sperm production.⁹ Enlarged ovaries with extensive follicular-type development have been observed in prepubertal calves intoxicated with locoweed.¹⁰ Cytoplasmic vacuolation is seen in luteal cells and in atretic follicles, which may affect normal progesterone and estrogen levels.¹¹ Cytoplasmic vacuolation of the pituitary may affect normal gonadotropin levels in both sexes, thereby influencing reproductive performance.¹²

Locoweed poisoning is a chronic condition requiring continuous ingestion for 4 to 6 weeks. Initially, cattle may be reluctant to graze locoweed, but once started, they become habituated, often seeking it out while excluding appropriate forage from their diet. Recovery is possible if cattle are removed from infested ranges and supplied with suitable feed before they become too emaciated. Some Astragalus locoweeds are perennials that thrive only during favorable environmental conditions.¹³ Flourishing and declining locoweed populations on western ranges are associated with the waxing and waning of reproductive and other acute and chronic disorders in indigenous cattle. Oxytropis locoweeds cause more consistent annual losses, coincident with more stable plant populations.

The toxic principle of locoweeds and the Swainsona genus of Australia is the indolizidine alkaloid swainsonine. Swainsonine interferes with oligosaccharide degradation and glycoprotein processing by inhibiting lysosomal α-mannosidase and mannosidase II. Resulting lesions are characterized microscopically by cytoplasmic vacuolation of cells in a variety of tissues.¹⁴ Because locoweed poisoning is an induced storage disease, postmitotic cells such as neurons and cardiac myocytes are most vulnerable. Involvement of these cells leads to clinical signs of central nervous system derangement (locoism) and heart failure. Vacuolar degeneration also is observed in other tissues, including the gonads, thyroid gland, pancreas, lymph nodes, and placenta. Lesions in the fetus are similar to those in the dam, presumably because swainsonine traverses the placental barrier.

In pregnant animals, both dam and fetus are affected, with abortion and teratogenic effects recorded. Locoweeds are unique in possessing a broad gestational window for the induction of toxic effects on the fetus. Abortion, the most common untoward effect, can occur at any stage of gestation after ingestion of locoweed for several weeks. Two cows dosed with Astragalus lentiginosus through a rumen fistula at 0.6 kg for the first 120 days of gestation aborted deformed fetuses by day 173.¹⁵ Skeletal malformations commonly include limb and joint abnormalities. The fetus normally is hypoxic and hypertensive relative to the dam because of fluid-filled lungs, with the fetus receiving oxygen from the placenta. Locoweed is thought to induce increased vascular resistance in the fetus, an effect similar to that in cattle at high elevations.¹ The increased workload on the fetal heart results in hypertrophy, dilatation, cardiac insufficiency, fluid accumulation, fetal death, and subsequent abortion. In ewes fed A. lentiginosus, serum progesterone and cotyledonary prostaglandin concentrations were altered¹⁶; presumably, cattle are affected in similar fashion. A dose-dependent reduction in serum progesterone concentration and a significant increase in cotyledonary prostaglandins were observed.

Real-time ultrasound imaging was used in the pregnant ewe model to demonstrate the adverse effects of locoweed on fetal growth and development.¹⁷ Ewes fed locoweed during gestational days 60 to 100 developed irregularly shaped cotyledons, with many of these structures becoming atretic. Excessive fluid accumulated in the placenta, leading to fetal heart arrhythmias. During dosing from days 60 to 70 of gestation, the heart rate in affected fetuses initially exceeded 200 beats per minute. With continued exposure to locoweed, fetal heart rate slowed to 60 beats per minute, and 3 days later fetal cardiac arrest occurred, followed by abortion in 40 to 72 hours. Fetal heart arrhythmias occurred concomitantly with cotyledon atrophy and hydrops allantois. Necropsy revealed fetal cardiomegaly. Similar fetal effects are thought to occur in cattle.

Effects of locoweed on the male reproductive tract have been studied in the ram; however, the effects can be extrapolated to other ruminant species. Spermatogenesis was decreased, and numerous cytoplasmic vacuoles have been reported in Sertoli cells, spermatogonia, and primary and secondary spermatocytes.¹⁸ Epithelium lining the epididymis, vas deferens, and seminal vesicles was severely hypertrophied and vacuolated. The lumen of the epididymis was practically devoid of sperm. Glandular tissue of the bulbourethral glands was mildly vacuolated.

Pine Needle Abortion

Needles from the Ponderosa pine tree (Pinus ponderosa), lodgepole pine (P. contorta), and common juniper (Juniperus communis) cause abortion primarily when consumed during the last trimester.¹⁹ Consumption by pregnant cows induces a premature parturition or abortion usually in 1 to 3 days but may be delayed for 2 to 3 weeks.²⁰ The greatest response from ingestion of pine needles occurs when ingested for a period of 3 days or more and at a relatively high level (>2 kg/day). Severe winter weather often leads to conditions in which cattle mingle under trees to escape wind and snow. Some calves from affected dams are born weak but may survive with adequate care. Common sequelae include retained fetal membranes and metritis. A study examining the effects of dietary variables on consumption of pine needles and parturition concluded that (1) feeding high levels of protein increased pine needle consumption but not abortion rate, (2) weathered or aged pine needles had activity equivalent to or greater than that of fresh needles, and (3) feeding corn silage to cows prevented pine needle consumption.

Isocupressic acid (ICA) is the abortifacient principle in Ponderosa and lodgepole pines, as well as in common juniper.¹⁹ It is contained in green or dry needles, bark, and branch tips. Isocupressic acid, like acetyl-ICA and succinyl-ICA, is classified as a labdane resin acid. All of these resin acids have induced abortions in cattle. The rumen microbes rapidly hydrolyze acetyl- and succinyl-ICA to ICA, the direct abortifacient. Isocupressic acid levels were 0.8% and 2.0% (dry weight) in lodgepole pine and common juniper, respectively.

The mechanism of pine needle abortion involves a profound constriction of the caruncular arterial bed.²¹ Furthermore, pine needle extracts and plasma from fed cows increased uterine arterial tone in vitro. After consumption of pine needles by beef cows in late gestation, uterine arterial blood flow progressively decreased to less than 50% of prefeeding rates before premature delivery of live weak calves. In another study, uterine blood flow in cows fed pine needles decreased progressively, declining to 25.5% of baseline by the day of premature parturition.²² The evidence suggests that consumption of pine needles induces a progressive reduction in uterine blood flow to the gravid horn and that this reduction causes the onset of premature parturition accompanied by normal prepartal changes in steroid secretion.

Broomweed

Perennial broomweeds or snakeweeds (Gutierrezia microcephala or Gutierrezia sarothrae) infest vast expanses of arid western rangelands. Although unpalatable, broomweed is one of the first green plants to emerge in the spring. Broomweed causes abortion or premature birth of weak calves. In affected herds, 10% to 60% of calves typically are involved. Of 52 cows fed G. microcephala, 23 cows delivered normal calves and 27 cows delivered premature, weak, or dead calves weighing 7.5 to 50 pounds. Broad gestational susceptibility of the fetus to broomweed is apparent from these early experiments. Thirty-four cows had placentas retained for 3 to 10 days after calving. Several cows had signs of systemic illness, and four either died or were euthanized. The toxicity of the broomweed varies according to growing conditions from year to year, stage of growth, and soil type.²³ Broomweed grown on sandy soil is more toxic than that grown on hard soils. The toxic principles in broomweed include mono- and diterpenes, saponins, oxygenated flavonol methyl esters, and yet-to-be-characterized saponins.²⁴ Specific abortifacients have not been identified.

Fescue

Fescue (Festuca arundinacea) toxicosis is caused by ingestion of fungus-infected (Neotyphodium coenophialum) tall fescue, mostly the Kentucky-31 cultivar. N. coenophialum is a seed-borne, intercellular, systemic fungus that resides in the leaf, sheaths, and flower of the grass host.²⁵ With 35 million (mostly fungus-infected) acres in the eastern and midwestern United States, the impact on bovine performance is enormous. Newer varieties of fescue have been developed that are free of the endophyte fungus. Unfortunately, the hardiness of this cool-season grass is considerably diminished in the absence of the fungus. Clearly, although it is toxic to cattle and other livestock, the fungus confers stress tolerance to the grass. Fungus-free fescue is less tolerant to weather-related and other stressors, including overgrazing. Cattle seem to like it more, but so do insects, nematodes, and plant pathogens.

The most critical consequence of feeding infected fescue in cow-calf operations is diminished reproductive efficiency. This condition usually is associated with a syndrome commonly referred to as “summer slump” and is pronounced when ambient temperature exceeds 32° C (89° F).²⁶ Toxic fescue forage fed to steers during the winter months did not cause health problems or reduction in performance; however, it did depress circulating PRL in a dose-dependent manner.²⁷ Clinical signs of summer fescue toxicosis are exacerbated by elevated environmental temperatures because of a decreased ability to dissipate excess body heat.²⁶ This is due largely to the peripheral vasoconstrictive effects of the toxic ergot peptide alkaloids (primarily ergovaline) produced by the endophyte fungus N. coenophialum. Adverse effects were recorded in two groups of cattle exposed to fescue containing 285 and 381 parts per billion (ppb), respectively, of ergovaline. The vasoconstrictive effects of another endophyte-produced compound, N-acetylloline, on the bovine lateral saphenous vein may contribute to fescue-associated problems.²⁸ These studies suggest possible additive effects of N-acetylloline and ergovaline and support the concept that a redistribution of blood flow to internal organs somehow compromises reproduction. Other signs associated with the summer toxicosis syndrome in general include slobbering, open-mouth breathing, reduced average daily gain, and a propensity to spend daytime hours in water or shade, rather than grazing. Fescue-induced hyperthermia also appears to be partly responsible for the decreased intensity of estrus and an increased embryolethality. This is consistent with the finding that bovine embryos incubated at 40° C for 48 to 60 hours suffer a dramatic increase in mortality.²⁹

Reduced calving rates are attributed to feeding endophyte-infected fescue.³⁰ Ninety-six percent of beef heifers raised on low-endophyte fescue (0% to 5% plants infected) conceived, compared with 55% of those raised on high-endophyte fescue (80% to 90% plants infected). Of primiparous cows grazing highly infected pastures, 33% conceived, versus 93% on low-endophyte pastures. Conception rates decreased 3.5% for each 10% increase in fungal infection. In a 3-year study, 39% of animals on high-endophyte fescue raised a calf, versus 65% of those on low-endophyte fescue pasture.³¹ The proportion of heifers with surviving calves was 11% with high-endophyte fescue versus 58% with low-endophyte fescue in the first-year, 63% versus 84% in the second year, and 42% versus 53% in the third year. First-service artificial insemination (AI) conception rates for the high-endophyte–exposed heifers were reduced for the first 2 years of the study (45% versus 74%)³²; however, the overall first-service conception rates among those cows inseminated for the 3-year period were 74% and 78% for the high- and low-endophyte groups, respectively.

Alterations in the hormonal milieu of cattle also are associated with infected fescue ingestion. Circulating prolactin (PRL) levels are depressed in cattle consuming infected fescue.³³ Dopamine is a known inhibitor of PRL secretion, and elevated circulating dopamine is associated with decreased serum PRL.³⁴ The dopamine-like activity of a toxic fescue diet is reflected by the significant depression in serum PRL within 48 hours after ingestion commences.²⁶ This biomarker of exposure is sustained regardless of ambient temperature effects, indicating that certain hormone levels are altered even in the absence of high environmental temperatures. Heat stress does appear to potentiate the adverse effects of infected fescue on reproductive function, however. McKenzie and Erickson³⁵ reported a 23% reduction in basal luteinizing hormone (LH) concentrations in heifers fed fescue hay. Other investigators, however, found no effect of endophyte-infected fescue on serum LH despite ergovaline intake at least 50% greater than the typical field exposure.³⁶ Altered luteal function was reported in 62% of heifers in which a corpus luteum was detected by ultrasonography.³⁷ Serum progesterone level was depressed and was unrelated to decreased average daily gain; however, it was prevented by high-energy supplementation. Puberty, as detected by the first sustained increase in serum progesterone, was delayed in Angus heifers raised on endophyte-infected fescue.³¹

These reports substantiate the adverse effects of toxic fescue on bovine reproductive function. Treatment of intoxicated cattle is neither practical nor economically feasible, and it is not particularly efficacious. Several mineral supplements have been touted as alleviating the clinical signs of fescue toxicosis. To date, little scientific evidence is available to support their efficacy. Slow-release formulations of thiabendazole³⁸ and ivermectin³⁹ obviate some of the adverse effects of the endophyte toxins. Thiabendazole has been shown to reduce some of the vasoconstrictive activity of toxic fescue. Enhanced reproductive performance, however, has not been demonstrated. Internal parasites do reduce forage intake in cattle, which translates into a reduction in gain. Work done by Dr. George Garner at the University of Missouri with cattle in environmental chambers indicates that parasites tend to lower the temperature threshold at which animals show signs of fescue toxicosis. The decreased sensitivity to summer fescue toxicosis, together with increased intake, may partially explain why dewormers improve performance. Metoclopramide, a dopamine receptor antagonist, was shown to increase the concentration of serum PRL, prolong grazing time, and maximize daily gain in steers ingesting toxic fescue.⁴⁰ Further research in these areas is necessary to demonstrate an effective cost-benefit ratio.

Toxic fescue pastures can be either renovated or managed; the decision is an economic one. To remove endophyte-infected fescue, the application of an effective herbicide is followed by a smother crop such as wheat or sudan grass, harvesting of the smother crop, and another application of herbicide if necessary.⁴¹ Cattle can be rotated off fescue during the hot summer months to increase gains. Toxic pastures also can be interseeded with legumes such as red clover, lespedeza, and birdsfoot trefoil for the dilution effect. Supplementation with corn at approximately 0.6% of body weight will allow efficient forage digestion and reduce the toxic effects of fescue. Avoiding the excessive application of nitrogen fertilizer reduces the concentration of ergovaline in toxic fescue. Application and type of fertilizer can be selected to encourage the growth of legumes. Cattle should not be permitted to graze the most toxic portion of infected fescue, the seedheads. Clipping or heavy grazing will prevent this from occurring. Finally, the ammoniation of toxic fescue hay is highly recommended to increase digestibility, reduce the toxic effects of ergovaline, and increase daily gains by 50% or more.