Selenium kinetics, placental transfer, and neonatal exposure in cynomolgus macaques (Macaca fascicularis)

Abstract

Forty pregnant cynomolgus macaques were treated daily from gestational day 20 to 50 by nasogastric intubation of 0, 25, 150, or 300 micrograms selenium as L-selenomethionine/kg body weight. In each group, 7-8 pregnancies were terminated by hysterotomy at gestational day 100 +/- 2 and the fetuses were examined, while 2-3 pregnancies in each group were allowed to proceed to term. Selenium and soluble glutathione peroxidase were measured in: maternal, neonatal, and fetal plasma and erythrocytes; fetal kidney, liver, muscle, and placenta; and maternal breast milk. The area under the multidose maternal plasma selenium concentration:time curve, the maximum maternal plasma selenium concentration, and the maternal urinary selenium excretion rates were proportional to the L-selenomethionine dose. Selenium concentrations in all fetal and neonatal, tissues were also proportional to maternal L-selenomethionine dose. Glutathione peroxidase was affected only in maternal erythrocytes, fetal kidney, and neonatal plasma. The selenium concentration in fetal plasma was an average 33% of that in maternal plasma. Although selenium concentrations in macaque milk were doubled by the highest dose, intrauterine selenium accumulation accounted for the majority of the neonatal selenium body burden. Despite the elevated selenium concentrations in fetal tissues, neonatal blood, and milk, no deleterious effects on neonates were observed. These results suggest that primate fetuses are well protected against selenium toxicity arising from high maternal L-selenomethionine intakes.

Chronic exposure to high doses of selenium in the first trimester of pregnancy: Case report and brief literature review

“…This single case does not allow us to draw conclusions on the effects of high doses of selenium on the fetus. However, considering the high doses received and the absence of side effects on the fetus, we could hypothesize that the placenta can prevent an excessive transfer of selenium to the fetus, in agreement with animal data by Hawkes et al ().…”

“…Animal experimental data are not conclusive: the selenium salts have been found to cross the placenta in hamsters (Willhite, Ferm, & Zeise, 1990) and rats (Bou-Resli, Mathew, Dashti, & Al-Zaid, 2002). However, in various animal species, including primates, the placenta seems to protect fetuses from selenium toxicity in case of maternal selenium poisoning (Hawkes et al, 1994). In mice, chronic exposure to selenium during pregnancy and lactation caused low birth weight and poor neonatal survival (Schroeder & Mitchener, 1971).…”

Selenium and breast-feeding

“…Se in fish fat can reach 59 % of the total amount found in muscle (Burger et al 1992). In mammals, experiments show that muscles of cynomologus macaques (Macaca fascicularis ) also have a higher concentration of Se than adipose tissue and a much higher capacity to retain supplemented Se (Hawkes et al 1994). In lactating women, urine Se is influenced by creatinine excretion and therefore by leanbody mass (Thomson et al 2001).…”

L-selenomethionine as a source of selenium added for nutritional purposes to food supplements

“…Despite elevated selenium concentrations in fetal tissues, neonatal blood and milk, no deleterious effects on neonates were observed. The authors suggested, based on these results, that primate foetuses are well protected against selenium toxicity arising from high maternal L-selenomethionine intakes (Hawkes et al, 1994).…”

“…In a study in pregnant female Macaques (Macaca fascicularis) administered Lselenomethionine (at a dose level providing 25, 150 and 300 µg selenium/kg bw/day) via nasogastric intubation during organogenesis, dose-dependent maternal toxicity as indicated by poor appetite and emesis was observed in the mid-and high-dose groups (Tarantal et al, 1991;Hawkes et al, 1994). The dose of 25 μg selenium/kg bw/day administered as Lselenomethionine was considered by the authors to produce no signs of selenium toxicity in the dams (a NOEL for maternal toxicity).…”