Examining the long-term impacts of ergot alkaloids on fetal heifer development and subsequent growth and reproductive performance.

Consumption of toxic endophyte-infected tall fescue (EI) results in poor reproductive performance in domestic livestock. In this study, the objective was to evaluate the effects of ergovaline exposure during mid-gestation (days 93 through 188 of gestation) on dam performance, the growing female fetus, and the subsequent growth and reproductive performance of the gestationally exposed heifer calves. Pregnant Angus and Simmental-Angus cows were blocked by age (2 to 3, to 7, and >7 y), body weight (BW), and breed; and then randomly assigned to graze either novel endophyte-infected tall fescue (EN; <5% infection rate; n = 27 year 1, n = 16 year 2) or toxic EI (99% infection rate; n = 27 year 1, n = 17 year 2). Weekly BW, body condition scores (BCS), hair coat scores, hair shedding scores (HSS), and blood samples for progesterone (P4) analysis were collected from mid-April through July of 2017 (year 1) and 2018 (year 2). Gestation length, birth weight, placental characteristics, heifer calf growth, onset of puberty, ovarian characteristics, and artificial insemination pregnancy rates were measured. Data were analyzed using the MIXED procedure of SAS. Cows grazing EI pastures had reduced average daily gain, reduced BCS, greater HSS, and decreased P4 concentrations compared to cows on EN pasture (P < 0.01). Birth weights were decreased for heifers whose dams were exposed to EI pastures during their second trimester (P < 0.01). Heifer pregnancy rates were not impacted by EI pasture exposure during gestation for either year of the study. However, a treatment-by-year effect was seen for the pregnancy rate for EI-exposed heifers in year 2; EI-exposed heifers in year 2 had increased pregnancy rates at two of the inseminations. Combined, these data reinforce that consumption of toxic EI during gestation can negatively impact both dam and offspring performance. More studies are needed to evaluate more parameters in an effort to elucidate the possible life-long impacts of ergovaline exposure during gestation.

The U.S. livestock industry incurs over one billion dollars of economic loss every year due to fescue toxicosis, caused by consuming ergot alkaloids produced by an endophytic fungus in some grass species. Identifying means to mitigate the negative effects of fescue toxicosis is needed for U.S. beef producers. Effective treatment for this toxicosis is still needed. The objective of this study was to evaluate the effects of ergovaline exposure during mid-gestation on dam performance, the growing female fetus, and the subsequent growth and reproductive performance of the gestationally exposed heifer calves. We identified specific phenotype traits that undergo developmental programming in utero in response to fescue toxicosis. However, measurements of growth and reproductive performance were not altered by ergot exposure.

Levodopa attenuates the feed intake reduction caused by ergot alkaloids in cattle.

Consumption of ergot alkaloids from endophyte-infected tall fescue results in losses to the livestock industry in many countries and a means to mitigate these losses is needed. The objective of this study was to evaluate intra-abomasal infusion of the dopamine precursor, levodopa (L-DOPA), on dopamine metabolism, feed intake, and serum metabolites of steers exposed to ergot alkaloids. Twelve Holstein steers (344.9 ±â€…9.48 kg) fitted with ruminal cannula were housed with a cycle of heat challenge during the daytime (32 °C) and thermoneutral at night (25 °C). The steers received a basal diet of alfalfa cubes containing equal amounts of tall fescue seed composed of a mixture of endophyte-free (E-) or endophyte-infected tall fescue seeds (E+) equivalent to 15 µg ergovaline/kg body weight (BW) for 9 d followed by intra-abomasal infusion of water (L-DOPA-) or levodopa (L-DOPA+; 2 mg/kg BW) for an additional 9 d. Afterward, the steers were pair-fed for 5 d to conduct a glucose tolerance test. The E+ treatment decreased (P = 0.005) prolactin by approximately 50%. However, prolactin increased (P = 0.050) with L-DOPA+. Steers receiving E+ decreased (P < 0.001) dry matter intake (DMI); however, when supplemented with L-DOPA+ the decrease in DMI was less severe (L-DOPA × E, P = 0.003). Also, L-DOPA+ infusion increased eating duration (L-DOPA × E, P = 0.012) when steers were receiving E+. The number of meals, meal duration, and intake rate were not affected (P > 0.05) by E+ or L-DOPA+. The L-DOPA+ infusion increased (P < 0.05) free L-DOPA, free dopamine, total L-DOPA, and total dopamine. Conversely, free epinephrine and free norepinephrine decreased (P < 0.05) with L-DOPA+. Total epinephrine and total norepinephrine were not affected (P > 0.05) by L-DOPA+. Ergot alkaloids did not affect (P > 0.05) circulating free or total L-DOPA, dopamine, or epinephrine. However, free and total norepinephrine decreased (P = 0.046) with E+. Glucose clearance rates at 15 to 30 min after glucose infusion increased with L-DOPA+ (P < 0.001), but not with E+ (P = 0.280). Administration of L-DOPA as an agonist therapy to treat fescue toxicosis provided a moderate increase in DMI and eating time and increased plasma glucose clearance for cattle dosed with E+ seed.

Fescue has become the dominant cool-season perennial grass in the southeastern region of the United States and is also found in other countries. Endophytes from a plant­fungus symbiotic relationship produce toxic alkaloids that have caused significant annual economic losses to the livestock industry. Treatments to alleviate this toxicosis are still demanded. This study evaluates the infusion of the dopamine precursor, levodopa (L-DOPA), to mitigate the toxicosis caused by ergot alkaloids. When L-DOPA was infused, eating duration increased and the decrease in feed intake caused by ergot alkaloids was less severe. Additionally, circulating dopamine and glucose clearance increased with L-DOPA. These results suggest that L-DOPA has the potential to aid in the mitigation of the toxicosis caused by ergot alkaloids.

5-hydroxytryphophan mitigates ergot alkaloid-induced suppression of serotonin and feed intake in cattle.

The impact of ergot toxicosis on livestock industries is detrimental and treatments are needed in many countries. The objective of this study was to evaluate the effects of acute exposure to ergot alkaloids and 5-hydroxytryptophan (5-HTP) supplementation on feed intake, serotonin metabolism, and blood metabolites in cattle. Eight Holstein steers (538 ±â€…18 kg) fitted with ruminal cannulas were used in a replicated 4 × 4 Latin Square design experiment with a 2 × 2 factorial treatment structure. The treatments were the combination of 0 (E-) or 15 µg ergovaline/kg BW (E+) and 0 (5HTP-) or 0.5 mg of 5-hydroxy-l-tryptophan/kg BW (5HTP+) administered daily for 6 d. Toxic endophyte-infected tall fescue seed was used to supply the daily dose of ergovaline. Endophyte-free seed was used to equalize seed intake between treatments. Ground seed was placed into the rumen immediately before feeding. The 5-HTP was dissolved in water and infused into the abomasum via the reticulo-omasal orifice. Blood was collected from a jugular vein catheter at 0, 1, 2, 4, 8, and 24 h after treatment administration. Ergovaline without 5-HTP (E+/5HTP-) decreased dry matter intake (DMI) in comparison to steers without ergovaline and 5-HTP (E-/5HTP-). However, 5-HTP infusion in association with ergovaline (E+/5HTP+) normalized the DMI. Although E + did not affect (P > 0.05) the area under the curve (AUC) of serum 5-HTP, 5-hydroxyindoleacetic acid, tryptophan, and kynurenine, serum and plasma serotonin concentrations were decreased (P < 0.05). The infusion of 5-HTP increased (P < 0.05) the AUC of serum 5-HTP, serum and plasma serotonin, and serum 5-hydroxyindoleacetic acid. In conclusion, acute exposure to ergot alkaloids reduced DMI and circulating serotonin in cattle but 5-HTP administration showed potential to normalize both circulating serotonin and feed intake.

Some grass species have a symbiotic relationship with an endophytic fungus that produces toxic ergot alkaloids which have detrimental impacts on herbivores. Ergot alkaloids have a significant impact on livestock production causing annual loss to the livestock industry that likely exceeds $1 billion. Effective treatment for this toxicosis is still needed. The objective of this study was to evaluate the effects of acute exposure to ergot alkaloids and 5-hydroxytryptophan supplementation on feed intake, serotonin metabolism, and blood metabolites in cattle. We found that 5-hydroxytryptophan administration has the potential to normalize both circulating serotonin and feed intake reduced by ergot alkaloid consumption.

Toxigenic Endophyte-Infected Tall Fescue and Ergot Alkaloids.

"Fescue toxicosis" and reproductive ergotism present identical toxidromes in late-gestational mares and, likely, other equids. Both toxic syndromes are caused by ergopeptine alkaloids (EPAs) of fungal origin, and they are collectively referred to as equine ergopeptine alkaloid toxicosis (EEPAT). EPAs are produced by either a toxigenic endophyte (Epichloë coenophiala) in tall fescue and/or a nonendophytic fungus (Claviceps purpurea), infecting small grains and grasses. EEPAT can cause hypoprolactinemia-induced agalactia/dysgalactia, prolonged gestation, dystocia, and other reproductive abnormalities in mares, as well as failure of passive transfer in their frequently dysmature/overmature/postmature foals. Prevention relies on eliminating exposures and/or reversing hypoprolactinemia.