Tryptophan metabolism in pregnant sheep: Increased fetal kynurenine production in response to maternal tryptophan loading

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/S0002-9378(99)70391-1 Byline: Trish Nicholls, Ilias Nitsos, David W. Walker Keywords: Excitotoxicity; fetus; kynurenine; kynurenic acid; neuroprotection; quinolinic acid; tryptophan; tryptophan 2,3-dioxygenase Abstract: Objective: The effects of a tryptophan load on the plasma concentration of kynurenine, the precursor for the production in the brain of the neuroactive products kynurenic acid and quinolinic acid, were determined in pregnant sheep at midgestation and late gestation and in nonpregnant sheep. Study Design: Pregnant ewes were given an intravenous infusion of 100 mg/kg L -tryptophan during 2 hours at 95 to 98 days' gestation (n = 4) or 135 to 138 days' gestation (n = 10). Nonpregnant ewes (n = 6) were studied in late estrus. Arterial blood samples taken from 2 hours before to 48 hours after the start of the infusion were used for analysis of plasma tryptophan, kynurenine, and cortisol concentrations. Results: Tryptophan loading at both gestational ages resulted in significantly greater increases in kynurenine concentrations in fetal plasma (at 95-98 days' gestation, from 5.7 [+ or -] 1.2 [mu]mol/L [baseline] to 247.9 [+ or -] 86.7 [mu]mol/L (peak); at 135-138 days' gestation, from 9.0 [+ or -] 2.3 [mu]mol/L [baseline] to 289.0 [+ or -] 194.0 [mu]mol/L [peak]) than in maternal plasma [at 95-98 days' gestation, from 4.6 [+ or -] 0.8 [mu]mol/L [baseline] to 118.0 [+ or -] 79.7 [mu]mol/L [peak]; at 135-138 days' gestation, from 4.8 [+ or -] 2.9 [mu]mol/L [baseline] to 98.3 [+ or -] 67.8 [mu]mol/L [peak]). It took longer for kynurenine concentrations to return to basal values in the fetus (24-30 hours) than in the ewe (8-12 hours). The kynurenine responses in pregnant and nonpregnant ewes were not different from each other. Conclusion: The production of kynurenine from tryptophan is significantly greater in the fetal lamb than in the pregnant or nonpregnant adult ewe. (Am J Obstet Gynecol 1999;181:1452-60.) Author Affiliation: Clayton, Victoria, Australia From the Department of Physiology, Monash University Article History: Received 12 February 1999; Revised 10 June 1999; Accepted 18 June 1999 Article Note: (footnote) [star] Supported by a grant from the National Health and Medical Research Council of Australia to D.W.W., [star][star] Reprint requests: David W. Walker, PhD, Department of Physiology, Monash University, Clayton, Victoria, Australia 3168., a 0002-9378/99 $8.00 + 0 6/1/100982