Ergot alkaloid exposure during gestation alters: II. Uterine and umbilical artery vasoactivity1

Klotz, J. L.; Britt, Jessica; Miller, M. F.; Snider, Miriam A; Aiken, Glen E.; Long, N. M.; Pratt, Scott L.; Andrae, John; Duckett, S. K.

doi:10.1093/jas/skz069

Cited by 19 publications

(23 citation statements)

References 37 publications

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“…Tall fescue seed was fed individually to supply 1.77 mg animal −1 d −1 of ergovaline and ergovalinine for E+ and the same weight of E− tall fescue seed was fed to supply 0 mg animal −1 d −1 of ergovaline and ergovalinine. Ergovaline and ergovalinine concentrations fed in this study were based on previous research and is detailed in Britt et al (2019). Ewes were individually penned into stalls (1.8 × 0.5 × 0.91 m) at 0700 and individually fed their respective treatment diet for 90 min.…”

Section: Experimental Designmentioning

confidence: 99%

“…Ewes within each group were fed equal amounts of TMR and seed daily to maintain similar feed intake across all treatments. Feed intake and body weight changes during the study are reported in Britt et al (2019). On day 133 of gestation, ewes underwent terminal surgery where fetuses were removed and euthanized.…”

Section: Experimental Designmentioning

confidence: 99%

“…On day 133 of gestation, ewes underwent terminal surgery where fetuses were removed and euthanized. Additional information on experimental design, ewe parameters and placental development are available in Britt et al (2019).…”

Section: Experimental Designmentioning

confidence: 99%

“…Darbysh] (E+; Lyons et al, 1986) and are responsible for vasoconstrictive events observed in fescue toxicosis (Strickland et al, 2011;Foote et al, 2012). Ergovaline has also been shown to be a potent vasoconstrictor in the bovine umbilical and uterine arteries (Dyer, 1993) and ovine (Klotz et al, 2019) and reduces blood flow to developing placental tissues and fetuses. Placental weight is highly correlated with fetal birthweight in cases of induced placental dysfunction such as hyperthermia (Alexander and Williams, 1971;Galan et al, 2005), maternal undernutrition (Wallace, 1948), and uteroplacental embolism (Lang et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Ergot alkaloid exposure during gestation alters: 3. Fetal growth, muscle fiber development, and miRNA transcriptome1

Greene

Britt

Powell

et al. 2019

Journal of Animal Science

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The objective of this study was to assess how exposure to ergot alkaloids during 2 stages of gestation alters fetal growth, muscle fiber formation, and miRNA expression. Pregnant ewes (n = 36; BW = 83.26 ± 8.14 kg; 4/group; 9 groups) were used in a 2 × 2 factorial arrangement with 2 tall fescue seed treatments [endophyte-infected (E+) vs. endophyte-free (E−)] fed during 2 stages of gestation (MID, days 35 to 85 vs. LATE, days 86 to 133), which created 4 possible treatments (E−/E−, E+/E−, E−/E+, or E+/E+). Ewes were individually fed a total mixed ration containing E+ or E− fescue seed according to treatment assignment. Terminal surgeries were conducted on day 133 of gestation for the collection of fetal measurements and muscle samples. Data were analyzed as a 2 × 2 factorial with fescue treatment, stage of gestation, and 2-way interaction as fixed effects. Fetuses exposed to E+ seed during LATE gestation had reduced (P = 0.0020) fetal BW by 10% compared with E− fetuses; however, fetal body weight did not differ (P = 0.41) with E+ exposure during MID gestation. Fetuses from ewes fed E+ seed during MID and LATE gestation tended to have smaller (P = 0.058) kidney weights compared with E− fetuses. Liver weight was larger (P = 0.0069) in fetuses fed E− during LATE gestation compared with E+. Fetal brain weight did not differ by fescue treatment fed during MID (P = 0.36) or LATE (P = 0.40) gestation. The percentage of brain to empty body weight (EBW) was greater (P = 0.0048) in fetuses from ewes fed E+ fescue seed during LATE gestation, which is indicative of intrauterine growth restriction (IUGR). Primary muscle fiber number was lower (P = 0.0005) in semitendinosus (STN) of fetuses exposed to E+ during MID and/or LATE gestation compared with E−/E−. miRNA sequencing showed differential expression (P < 0.010) of 6 novel miRNAs including bta-miR-652_R+1, mdo-miR-22-3p, bta-miR-1277_R-1, ppy-miR-133a_L+1_1ss5TG, hsa-miR-129-1-3p, and ssc-miR-615 in fetal STN muscle. These miRNA are associated with glucose transport, insulin signaling, intracellular ATP, hypertension, or adipogenesis. This work supports the hypothesis that E+ tall fescue seed fed during late gestation reduces fetal weight and causes asymmetrical growth, which is indicative of IUGR. Changes in primary fiber number and miRNA of STN indicate that exposure to E+ fescue fed during MID and LATE gestation alters fetal muscle development that may affect postnatal muscle growth and meat quality.

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Section: Experimental Designmentioning

confidence: 99%

Section: Experimental Designmentioning

confidence: 99%

Section: Experimental Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ergot alkaloid exposure during gestation alters: 3. Fetal growth, muscle fiber development, and miRNA transcriptome1

Greene

Britt

Powell

et al. 2019

Journal of Animal Science

Self Cite

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“…In contrast, solute carrier family 22 member 9 (SLC22A9; also known as OAT7) experienced a 5-fold increase in the cotyledon from E+/E+ ewes and was previously thought to be liver-specific [62]. It has been hypothesized that ergot alkaloids or metabolites may cross the placental barrier [7] but no research is available documenting the presence of these compounds in the fetus or which transport systems may be involved if placental transport exists. It was previously proposed that the downregulation of certain transport systems may augment fetal exposure to environmental toxicants during pregnancy [63].…”

Section: Gene Ontology and Kegg Pathway Analysismentioning

confidence: 99%

Differentially expressed genes in cotyledon of ewes fed mycotoxins

2020

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Background Ergot alkaloids (E+) are mycotoxins produced by the endophytic fungus, Epichloë coenophiala, in tall fescue that are associated with ergotism in animals. Exposure to ergot alkaloids during gestation reduces fetal weight and placental mass in sheep. These reductions are related to vasoconstrictive effects of ergot alkaloids and potential alterations in nutrient transport to the fetus. Cotyledon samples were obtained from eight ewes that were fed E+ (n = 4; E+/E+) or E- (endophyte-free without ergot alkaloids; n = 4; E−/E-) seed during both mid (d 35 to 85) and late (d 85–133) gestation to assess differentially expressed genes associated with ergot alkaloid induced reductions in placental mass and fetal weight, and discover potential adaptive mechanisms to alter nutrient supply to fetus. Results Ewes fed E+/E+ fescue seed during both mid and late gestation had 20% reduction in fetal body weight and 33% reduction in cotyledon mass compared to controls (E−/E-). Over 13,000 genes were identified with 110 upregulated and 33 downregulated. Four genes had a |log2FC| > 5 for ewes consuming E+/E+ treatment compared to controls: LECT2, SLC22A9, APOC3, and MBL2. REViGO revealed clusters of upregulated genes associated glucose, carbohydrates, lipid, protein, macromolecular and cellular metabolism, regulation of wound healing and response to starvation. For downregulated genes, no clusters were present, but all enriched GO terms were associated with anion and monocarboxylic acid transport. The complement and coagulation cascade and the peroxisome proliferator-activated receptor signaling pathway were found to be enriched for ewes consuming E+/E+ treatment. Conclusions Consumption of ergot alkaloids during gestation altered the cotyledonary transcriptome specifically related to macronutrient metabolism, wound healing and starvation. These results show that ergot alkaloid exposure upregulates genes involved in nutrient metabolism to supply the fetus with additional substrates in attempts to rescue fetal growth.

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The C-8-S-isomers of ergot alkaloids — a review of biological and analytical aspects

Cherewyk,

Blakley,

Al-Dissi

2023

Mycotoxin Res

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Ergot alkaloids are secondary metabolites that are produced by fungi and contaminate cereal crops and grasses. The ergot alkaloids produced by Claviceps purpurea are the most abundant worldwide. The metabolites exist in two configurations, the C-8-R-isomer (R-epimer) and the C-8-S-isomer (S-epimer). These two configurations can interconvert to one another. Ergot alkaloids cause toxic effects after consumption of ergot-contaminated food and feed at various concentrations. For bioactivity reasons, the C-8-R-isomers have been studied to a greater extent than the C-8-S-isomer since the C-8-S-isomers were considered biologically inactive. However, recent studies suggest the contrary. Analytical assessment of ergot alkaloids now includes the C-8-S-isomers and high concentrations of specific C-8-S-isomers have been identified. The inclusion of the C-8-S-isomer in regulatory standards is reviewed. This review has identified that further research into the C-8-S-isomers of ergot alkaloids is warranted. In addition, the inclusion of the C-8-S-isomers into regulatory recommendations worldwide for food and feed should be implemented. The objectives of this review are to provide an overview of historic and current studies that have assessed the C-8-S-isomers. Specifically, this review will compare the C-8-R-isomers to the C-8-S-isomers with an emphasis on the biological activity and analytical assessment.

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Ergot alkaloid exposure during gestation alters: II. Uterine and umbilical artery vasoactivity1

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Cited by 19 publications

References 37 publications

Ergot alkaloid exposure during gestation alters: 3. Fetal growth, muscle fiber development, and miRNA transcriptome1

Ergot alkaloid exposure during gestation alters: 3. Fetal growth, muscle fiber development, and miRNA transcriptome1

Differentially expressed genes in cotyledon of ewes fed mycotoxins

The C-8-S-isomers of ergot alkaloids — a review of biological and analytical aspects

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