311. Mitigation Strategies for Ergot Alkaloid-induced Vasoconstriction: Effects of 5-hydroxytryptophan on Maternal and Fetal Development, and Fetal Liver Metabolomics.

Abstract To evaluate the maternal and fetal effects of ergot alkaloids and 5-hydroxytryptophan (5-HTP) consumed during gestation, pregnant ewes carrying twins were randomly assigned to one of three treatments: 1) negative control (CON, n = 10), 2) 5HTP (2.5 mg/kg BW) and toxic tall fescue seed containing 1.77 mg ewe-1 d-1 ergovaline/ergovalinine (E+/5-HTP, n = 10), or 3) positive control, fed toxic tall fescue seed containing 1.77 mg ewe-1 d-1 ergovaline/ergovalinine (E+, n = 10). Ewes were individually fed TMR plus treatment (CON, E+/5-HTP, or E+) at 2.5% of body weight from gestation d (gd) 86 to d 111. On d 111, a terminal necropsy was performed on the ewes to collect placental weights, fetal measurements, and fetal liver tissue for metabolomics analyses. Dry matter intake did not differ between E+/5-HTP or E+ versus CON and averaged 2.48% BW. Average daily gain did not differ between E+/5-HTP or E+ versus CON and averaged 0.304 kg/d during this study. Serum glucose and plasma insulin concentrations in ewes at gd85 and gd111 did not differ by treatment. Serum NEFA concentrations were greater (P < 0.05) for CON than E+/5-HTP or E+ on gd111 but did not differ on gd85. Plasma IL-6, a proinflammatory cytokine, concentration was greater (P < 0.05) in E+ ewes compared to CON on gd85. Gravid uterus weight per ewe was lower (P < 0.05) for E+ compared to CON. Exposure to ergovaline (E+) during gestation reduced (P = 0.036) total fetal weight per ewe compared to CON; however, total fetal weight per ewe did not differ with supplementation of 5-HTP (E+/5-HTP) compared to CON. Total placentome number and weight did not differ between treatments. Individual fetal weight was greater (P = 0.0033) for CON than E+; however, fetal weight did not differ (P = 0.22) between CON and E+/5-HTP. Fetal heart weight was lower (P = 0.013) for E+ compared to CON and tended to be lower (P = 0.052) for E+/5-HTP than CON. Fetal liver weight was greater (P < 0.05) for CON than E+ or E+/5-HTP. Fetal kidney and pancreas weights tended to be lower (P < 0.10) for E+ compared to CON but did not differ (P > 0.10) between E+/5-HTP and CON. Metabolomic analyses of fetal liver showed that E+ exposure during fetal liver development up-regulated 190 and down-regulated 628 metabolites compared to CON involved in biosynthesis of secondary compounds and amino acids. E+/5-HTP fetal livers had 407 up- and 55 down-regulated metabolites compared to E+ which included metabolic pathways and biosynthesis of secondary compounds. Supplementation of 5-HTP to pregnant ewes fed toxic tall fescue (E+) seed mitigated the negative effects of E+ on maternal oxidative stress, and fetal growth and organ development.