Ergot alkaloid consumption alters serotonin receptor-induced vasoactivity in ovine umbilical vasculature

Authors: Klotz, James; DUCKETT, SUSAM - Clemson University; BRITT, JESSI - Clemson University; GREENE, MASLYN - Clemson University; KENT-DENNIS, CORAL - Oak Ridge Institute For Science And Education (ORISE)

Submitted to: Human and Experimental Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/10/2024
Publication Date: N/A
Citation: N/A

Interpretive Summary: When livestock graze tall fescue they can be exposed to ergot alkaloids. Ergot alkaloids are toxins produced by a fungus that is present in the grass and are responsible for the fescue toxicosis syndrome. When pregnant livestock consume ergot alkaloids there is negative effect on fetal growth and development. Some of this has been associated with a reduction in umbilical blood flow. Contraction and relaxation of umbilical blood vessels is regulated in part by serotonin. Ergot alkaloids are capable of binding to serotonin receptors and disrupting their normal functions. This study sought to understand the role that different serotonin receptor have on causing contraction of umbilical artery and vein and how this is affected by ergot alkaloids. Of the serotonin receptors evaluated only one was responsible for stimulating contraction and its function was altered in the ergot alkaloid treatment. Also, the umbilical serotonin receptor activity decreased as the length of gestation increased. This research will be primarily of interest to other researchers looking to better understand the mechanisms by which ergot alkaloids negatively effect fetal growth and development.

Technical Abstract: Consumption of ergot alkaloids during the second half of gestation have been shown to decrease umbilical artery vasoactivity resulting in lower birth weights. The negative vascular effects of ergot alkaloids are mediated predominantly through serotonergic and adrenergic receptors in other tissues. The objective was to evaluate the vasoactivity of serotonin (5-HT) receptors 5-HT2A and 5-HT1B/1D in the umbilical artery and vein from ewes receiving endophyte-infected (E+ 1.77 mg ergovaline/hd/d) or endophyte-free (E-; 0 mg ergovaline/hd/d) tall fescue seed at d 110 (n=4 E+; n=4 E-) and d 133 (n=3 E+; n=3 E-) of gestation. Suffolk ewes began receiving seed treatments on d 86 of gestation. Gravid reproduction tracts were collected from ewes at slaughter. The umbilical cord from the first exteriorized fetus was ligated and placed in Krebs-Henseleit buffer. Umbilical arteries and veins were cleaned of excess adipose and connective tissue and stored in Krebs-Henseleit buffer at 4' C until initiation of myograph experiments the following day. Two mm cross sections of each blood vessel were luminally mounted in multi-myographs containing 5 mL of continuously oxygenated Krebs-Henseleit buffer and exposed to a reference dose of 120 mM KCL followed by increasing concentrations of rizatriptan benzoate (5-HT1B/1D agonist) and TCB-2 (5-HT2A agonist) that ranged from 5x10-9 M to 1x10-4 M. The 5-HT1B/1D agonist did not stimulate a contractile response in either the umbilical artery or vein for any gestation time point evaluated. The 5-HT2A agonist caused large contractile responses in the umbilical artery with the greatest occurring at d 110 and decreasing in magnitude as days of gestation increased (P<0.05). On d 110 and 133 of gestation, umbilical arteries from ewes receiving E- seed had a greater contractile response than those arteries collected from ewe receiving the E+ treatment (P<0.05). The umbilical vein also responded to increasing concentrations of the 5-HT2A agonist. The maximal response of the umbilical vein on d 110 of gestation was greater than d 133 when exposed to 5-HT2A agonist (P<0.05). Unlike the artery, umbilical veins from ewes receiving E+ seed had greater contractile response than E- at d 133 (P<0.05). These results demonstrate that the vascular smooth muscle contractions of the umbilical artery and vein are induced by 5-HT2A receptor activity and not 5-HT1B/1D. Umbilical artery 5-HT2A receptor activity responded to seed treatment differently than umbilical vein and could be the source of ergot alkaloid-induced intra-uterine growth restriction observed when ewes graze toxic tall fescue during gestation.