354. Impact of Circulating Ergovaline and 5-hydroxytryptophan on Umbilical Vascular Activity and Select Gene Expression in Sheep.

Abstract To determine effects of ergovaline and the serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) have on umbilical vascular activity and gene expression, 27 pregnant ewes were exposed to 3 different dietary treatments during gestation. Ewes were individually fed a total mixed ration (TMR) daily with no ergovaline (CON; n = 9), TMR containing 1.77 mg ergovaline/kg BW (E+; n = 9), or TMR containing 1.77 mg ergovaline/kg BW/day plus 2.5 mg 5-HTP/kg BW (E+/5-HTP; n = 9) daily from d86 to d111 of gestation. Jugular blood was collected on d78, 85, 92, 99, and 111 of gestation. On d112 umbilical cord and fetal blood were collected at necropsy. Umbilical arteries and veins were cleaned of perivascular adipose and connective tissues and frozen for genomic analyses or sliced and luminally mounted in a multimyograph to assess contractility to increasing concentrations of 5-HT, 5-HTP, ergovaline, 5-HT2A receptor agonist (TCB), or endothelin. Whole blood was analyzed for ergovaline, and serum and plasma were analyzed for 5-HT, 5-HTP, and 5-hydroxyindoleacetic acid (5-HIAA). Isolated umbilical artery and vein RNA was used to quantify expression of genes of interest associated with serotonin and endothelin using qPCR. Data were analyzed as randomized complete block for ewe treatment using mixed models of SAS. After d86, concentrations of ergovaline were greater in E+ and E+/5HTP blood than CON (P < 0.05) which remained at or below limit of detection (LOD; 10 pM). On d112, fetal blood collected from E+ and E+/5-HTP treatments had greater ergovaline concentrations than CON (P < 0.05), which remained below LOD. Serum and plasma 5-HTP and 5-HIAA were greater in E+/5HTP ewes compared to E+ and CON (P < 0.05), but there was no difference in serum or plasma 5-HT between any treatment groups. 5-HTP did not cause vascular contraction in umbilical artery or vein in any treatment (P > 0.05). Contractile response to 5-HT was lower in E+ umbilical artery than CON and E+/5-HTP, but E+/5-HTP was greater than E + (P< 0.05). Umbilical artery response to TCB was greatest for CON and lowest for E + (P< 0.05), with no difference between any treatment in response to ergovaline. CON and 5-HTP/E+ tended (P = 0.09) to have greater umbilical artery response to endothelin compared to E+. No differences were found in contractile response of umbilical vein to any compound evaluated. Neither the E+ or E+/5-HTP treatment affected expression of genes associated with serotonin or endothelin signaling in umbilical artery or vein. These data are first to demonstrate the presence of circulating ergovaline associated with a dietary treatment and first to demonstrate ergovaline crossing to the fetal side of the placenta. Supplementation of 5-HTP appeared to mitigate negative effects of ergovaline on serotonin and endothelin regulation of vasoactivity and is an effective tool for offsetting negative effects of ergotism.