Fetal growth retardation and death in pantothenic acid-deficient rats is due to imparired placental function

Abstract

Maternal pantothenic acid (PA) deficiency in rats leads to retarded fetal growth, congenital malformation, and fetal death. The teratogenic effect was reported in mild maternal PA deficiency. We investigated if the adverse outcome of pregnancy in PA deficiency was caused by impaired placental development of functions. Sprague-Dawley pregnant rats (200 to 240 g) were pair-fed AIN-76 purified diets with (controls) or without PA for 3 weeks. We determined the body and organ weights, and PA status of pups and dams; resorption rate, weight and DNA content of placenta; and maternal plasma concentration of progesterone, and placental acetylcholine concentration relative to the placental function. The dams in the PA-deficient group had body and organ weights comparable to the control, produced pups with lower body and organ weights, and had higher resorption rates (57% versus 15%) than the control. The pups were more seriously affected by PA deficiency than the dams, with significantly lower PA and CoA concentration in organs compared with the control pups. Compared with the control, PA-deficient dams had on day 5 of pregnancy, a lower plasma progesterone concentration (x ± SEM: 89.3 ± 8.3 versus 118.3 ± 10.5 nmol/L, P < 0.05), and elevated plasma cholesterol (2.57 ± 0.21 versus 1.61 ± 0.11 mmol/L, P < 0.05), and on day 15 of pregnancy, elevated placental cholesterol concentration (4.03 ± 0.08 versus 3.54 ± 0.05 μmol/g wet, P < 0.05), a lower placental acetylcholine concentration (1.32 ± 0.07 versus 1.54 ± 0.03 nmol/g wet P < 0.05), and lower placental PA (free and total) and CoASH concentration. Placental weight and DNA content did not differ significantly between the groups. We conclude that the combination of impaired placental endocrine functions and an inadequate supply of PA for fetal growth explain the retarded fetal growth and death, and more adverse effect to pups than to dams.