Selenium and at-risk pregnancy: challenges and controversies

Abstract

Selenium (Se), an essential trace element, is inserted as selenocysteine into an array of functional proteins and forms the core of various enzymes that play a cardinal role in antioxidant defense mechanisms, in redox regulation, and in thyroid hormone metabolism. Variations in plasma Se are due to nutritional habits, geographic and ethnic differences, and probably to genetic polymorphisms, the latter still to be conclusively established. Se concentrations were reported to be low in women of reproductive age in the UK, decreasing further during pregnancy, this resulting in low plasma and placental antioxidant enzyme activities. Since low serum Se levels have been found in women with preeclampsia, it has been hypothesized that low maternal Se status during early gestation may be an indicator of preterm birth. Moreover, it is documented that Se administration during pregnancy tendentially reduced the markers of thyroid autoimmunity and the incidence of maternal hypothyroidism in the postpartum period. Importantly, low Se levels in pregnant women affect fetal growth and augment the risk of delivering a small-for-gestational age infant by reducing placental antioxidant defense, while low Se in the third trimester is thought to indicate increased demands by the placenta, an issue which requires further confirmation. There is evidently a need for double-blind, placebo-controlled studies to better determine the efficacy and safety of Se supplementation in pregnancy at high risk for complications, and for measurement of Se levels or of selenoprotein P, the most reliable parameter of Se status, particularly in selenopenic regions.

Keywords: Miscarriage; Preeclampsia; Pregnancy; Premature birth; Selenium; Selenomethionine; Selenoprotein-P; Selenoproteins; Thyroid autoimmunity.

Fig. 1

Selenoproteins and their actions

Fig. 2

The main metabolic steps of metabolism of inorganic and organic Se Both inorganic (selenite) and organic (selenomethionine, SeMet) are converted to selenide (H₂ Se) before the formation of selenocysteine (SeCys) and its insertion in bioactive selenoproteins.

Fig. 3

Uterine arterial hypoxia, or placental ischemia, triggers oxidative stress (OS), generating superoxide radical (O₂ ^*) as a byproduct by specific enzymes such as xanthine or nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. O₂ ^* may stimulate the production of cytokines (particularly IL-6), thus increasing the intensity of OS and inflammation and further increasing the generation of O₂ *_, leading to such adverse pregnancy outcomes as altered placental growth, reduced fetoplacental blood flow, and preeclampsia. Sufficient availability of Se may alleviate OS by increasing antioxidant capacities, such as superoxide dismutase (SOD) which converts O₂ * to hydrogen peroxide (H2O2), and inhibiting cytokine formation and activity