Dietary arginine supplementation during early pregnancy enhances embryonic survival in rats

Four experiments were conducted with 120 pregnant Sprague-Dawley rats to determine effects of dietary arginine supplementation on embryonic survival. Rats were fed a nonpurified diet supplemented with 1.3% (wt:wt) L-arginine-HCl or 2.2% (wt:wt) L-alanine (isonitrogenous control) throughout pregnancy (Expt. 1), between d 1 and 7 of gestation and then the nonpurified diet until parturition (Expt. 2), between d 1 and 7 of gestation for determining the number of surviving embryos on d 7 (Expt. 3), or between d 1 and 4 of pregnancy for blood sampling on d 5 after overnight food deprivation (Expt. 4). Litter size increased (P < 0.01) in response to arginine supplementation throughout pregnancy (14.5 +/- 0.62 vs. 11.3 +/- 0.61) or during the first 7 d of pregnancy (14.7 +/- 0.33 vs. 11.3 +/- 0.37). The number of surviving embryos was greater (P < 0.01) when arginine was supplemented between d 1 and 7 of pregnancy (14.7 +/- 0.39 vs. 11.4 +/- 0.66). Concentrations of nitric-oxide metabolites, arginine, proline, glutamine, and ornithine were higher (P < 0.05), but urea levels were lower (P < 0.05) in the serum of arginine-supplemented rats compared with the control group. The arginine treatment increased (P < 0.05) protein levels for inducible and constitutive nitric-oxide synthase at implantation sites by 35-37%. These results indicate that dietary arginine supplementation enhances embryonic survival, therefore increasing litter size by 30% at term birth. This novel finding has important implications for preventing early pregnancy loss and enhancing reproductive performance in mammals.