Effect of 25 - hydroxyvitamin D 3 and 1 , 25 - dihydroxyvitamin D 3 maternal loads on maternal and fetal vitamin D metabolite

Two groups of female rats were used to investigate vitamin D metabolism in the pregnant animals and in their fetuses. In the first group, 3 wg of 25-hydroxyvitamin D3 (25-OH-D 3) per kg of body weight were injected into intact or nephrectomized (NX) pregnant rats 3 h before sacrifice on day 21 of pregnancy ; in the second group, 2 and 6 ng, respectively, of 1,25-dihydroxyvitamin D3 (1,2510H1 2) per day were infused continuously into pregnant rats between days 17 and 21 of pregnancy. The findings in the fetuses were obtained by quantitative analysis of extracts (Extrelut) of total fetal body lipids ; the extracts were purified on Sep Pak and vitamin D sterols were further separated by high-pressure liquid chromatography. Three hours after the dams were injected with 25OH-D 3, the maternal plasma concentration (mean + SD) of 1,2510H) ZD3was 221 ± 84 pg/ml. In NX pregnant rats, the 1,2510HI ZD3levels were still elevated : 95.6 + 49.0 pg/ml vs 45 ± 22 pg/ml in control rats. In fetuses from intact or NX dams, the levels of 25-OH-D 3 and 1,25(OH) D3were not different from the results obtained in the control fetuses but 24,25(OH) concentrations were increased (6.7 + 1.2 ng vs 2.2 ± 0.7 ng/g body weight). After maternal infusion of 2 or 6 ng/day of 1,25(OHI ZD3(n = 8), plasma concentrations (mean + SD) of the metabolite were 64+31 and 517 + 356 pg/ml, respectively, the second being significantly higher than that of the control rats ; 25-OH-D and 24,25(OH) D3levels did not change. 1,2510H1 D3contents (mean ± SD) in fetuses from the treated dams were not different from those of control fetuses 110 ± 2 pg/g body weight). Our results suggest that pregnant rats and their fetuses were protected against an excessive increase of 1,2510H) D3concentrations in the maternal plasma ; although there was some individual hypercalcemia, no significant increase in mean calcemia was detected in the dams, and 1,25(OH) D3either did not cross the placental barrier or was rapidly metabolized because we did not find any changes in the fetal content. As in intact or NX pregnant rats, 25-OH-D 3was metabolized into 1,2510H) ZD3the increase of 24,25(OH) D3in the fetuses might be associated with a protective mechanism.