Selenium in reproductive health

doi:10.1016/j.ajog.2011.07.034

American Journal of Obstetrics and Gynecology

Volume 206, Issue 1, January 2012, Pages 21-30

https://doi.org/10.1016/j.ajog.2011.07.034 Get rights and content

Selenium is an essential trace element of importance to human biology and health. Increasing evidence suggests that this mineral plays an important role in normal growth and reproduction in animals and humans, and selenium supplementation is now recommended as part of public health policy in geographical areas with severe selenium deficiency in soil. This review addresses the biological functions of selenium followed by a detailed review of associations between selenium status and reproductive health. In many countries, selenium dietary intake falls below the recommended nutrient intakes and is inadequate to support maximal expression of the selenoenzymes. Numerous reports implicate selenium deficiency in several reproductive and obstetric complications including male and female infertility, miscarriage, preeclampsia, fetal growth restriction, preterm labor, gestational diabetes, and obstetric cholestasis. Currently, there is inadequate information from the available small intervention studies to inform public health strategies. Larger intervention trials are required to reinforce or refute a beneficial role of selenium supplementation in disorders of reproductive health.

Section snippets

Selenium, amino acids, and selenoproteins

Dietary selenium, initially taken up from the soil and concentrated by plants, is absorbed in the small intestine and incorporated into proteins by complex mechanisms that remain unclear.⁴ Selenite (SeO₃²⁻; inorganic form of selenium) crosses the plasma membrane and reacts with cytoplasmic thiols in the reduction pathway; this forms selenide, which is then methylated, giving rise to methylated selenium derivatives that are excreted in urine, expired air via the lungs, and feces (Figure 1).5, 6

Dietary selenium

Plant foods are the major dietary sources of selenium in most countries.18, 19 Wheat is the most efficient selenium accumulator of the common cereals and is 1 of the most important selenium sources for man.4, 20 The content in food depends on the selenium content of the soil in which plants are grown or animals are raised. For example, the selenium content in the soil of the high plains of northern Nebraska and the Dakotas is very high, and the inhabitants have the highest selenium intakes in

Selenium deficiency

Selenium deficiency as assessed by dietary intake and/or blood selenium concentrations has been identified in people inhabiting geographical regions notable for low soil selenium content, such as volcanic regions.15, 25 Human selenium deficiency diseases have been recognized in China and Tibet.26, 27 Keshan disease, a reversible endemic cardiomyopathy, is characterised by focal myocardial necrosis often associated with inflammatory infiltrates and calcification.

The disorder is exclusively

Selenium toxicity

There is also a moderate to high health risk of selenium toxicity, first discovered in animals grazing in areas with high selenium content in the soil.³⁸ Chronic toxicity of selenium in humans results in selenosis, a condition characterized by brittleness or loss of hair and nails, gastrointestinal problems, rashes, garlic breath odor, and nervous system abnormalities.³⁹

In China, it has been reported that selenosis occurs with increased frequency in people who consumed selenium at levels above

Male fertility

Selenium is essential for testosterone biosynthesis and the formation and normal development of spermatozoa.44, 45 Testicular tissue contains high concentrations of selenium, predominantly as GPx4, and this provides the link between selenium, sperm quality, and male fertility because GPx4 is a fundamental determinant of the architecture of the spermatozoan midpiece14, 46 and is considered to shield developing sperm cells from oxidative DNA damage.47, 48 ROS have been implicated in male

Selenium and normal pregnancy

The growing fetus requires selenium. Selenium is transported across the placenta by passive diffusion down a concentration gradient.⁶² Decidual selenium concentrations are higher than endometrial,⁶³ whereas umbilical venous concentrations of selenium are lower than maternal.⁶⁴ In countries such as Poland and Yugoslavia in which soil selenium content and dietary intake are low, maternal selenium concentrations and GPx activity fall during pregnancy, being the lowest at delivery compared with

Miscarriage

Miscarriage, a clinically detectable pregnancy that fails to progress past 24 weeks' gestation, occurs in 10-20% of all pregnancies.⁶⁹ Genetic (chromosomal) abnormalities explain at least half of all miscarriages. Although anatomical, endocrine, immune, infective, and thrombophilic conditions are other possible causes, most chromosomally normal miscarriages remain unexplained or idiopathic.⁷⁰

In humans, a UK observational study reported significantly lower serum selenium concentrations in 40

Conclusions

There are wide differences in selenium intake across diverse populations, depending on the selenium content of the soil and hence the selenium content in staple foodstuffs as well as on variations in individuals' diets. Evidently the balance between intake, tissue concentration, and selenoenzyme synthesis is a very delicate one. This review illustrates the potential influence that selenium status has on many disorders relating to both animal and human reproduction and pregnancy.

An important

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Successful male fertilization requires the main processes such as normal spermatogenesis, sperm capacitation, hyperactivation, and acrosome reaction. The progress of these processes depends on some endogenous and exogenous factors. So, the optimal level of ions and essential and rare elements such as selenium, zinc, copper, iron, manganese, calcium, and so on in various types of cells of the reproductive system could affect conception and male fertility rates. The function of trace elements in the male reproductive system could be exerted through some cellular and molecular processes, such as the management of active oxygen species, involvement in the action of membrane channels, regulation of enzyme activity, regulation of gene expression and hormone levels, and modulation of signaling cascades. In this review, we aim to summarize the available evidence on the role of trace elements in improving male reproductive performance. Also, special attention is paid to the cellular aspects and the involved molecular signaling cascades.
Parental treatment with selenium protects Caenorhabditis elegans and their offspring against the reproductive toxicity of mercury
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Mercury (Hg) is one of the major pollutants in the environment, which requires effective countermeasures to manage its risk to both human health and the ecosystem. The antagonistic effect of selenium (Se) against methyl mercury (MeHg) and HgCl₂ was evaluated using parent and offspring Caenorhabditis elegans (C. elegans) in this study. Through designated acute exposure of 24 h, our results showed that both MeHg and HgCl₂ induced dose-dependent reproductive toxicity, including increased germ cell apoptosis, decrease in the number of oocytes, brood size, and sperm activation. The increased germ cell apoptosis was even higher in F1 and F2 generations, but returned to control level in F3 generation. Pretreatment with Se significantly suppressed the reproductive toxicity caused by Hg in both parental worms and their offspring, but had little influence on Hg accumulation. The protective role of Se was found closely related to the chemical forms of Hg: mtl-1 and mtl-2 genes participated in reducing the toxicity of HgCl₂, while the gst-4 gene was involved in the reduced toxicity of MeHg. The formation of Se-Hg complex and the antioxidant function of Se were considered as possible antagonistic mechanisms. Our data indicated that pretreatment with Se could effectively protect C. elegans and their offspring against the reproductive toxicity of Hg in different chemical forms, which provided a reference for the prevention of Hg poisoning and essential information for better understanding the detoxification potential of Se on heavy metals.
Serum selenium, selenoprotein P, and glutathione peroxidase 3 during early and late pregnancy in association with gestational diabetes mellitus: Prospective Odense Child Cohort
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Diet is an important modifiable risk factor for gestational diabetes mellitus (GDM) and its related complications; however, the role of essential micronutrients such as selenium (Se), particularly in populations with low Se intake, is inconclusive.
The aim was to investigate the association of 3 established biomarkers of Se status with GDM, gestational glucose metabolism, and large for gestational-age offspring.
This study included 1346 pregnant females with 2294 serum samples from the prospective, population-based Odense Child Cohort study, Denmark. Serum Se, selenoprotein P (SELENOP) concentrations, and glutathione peroxidase 3 (GPX3) activity were measured in early and late pregnancy, and fasting glucose and insulin assessments in late pregnancy. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated, and the GDM definition was according to the WHO 2013 threshold of fasting venous plasma glucose of ≥5.1 mmol/L. A subcohort underwent an oral glucose tolerance test. Regression models adjusted for various confounders quantified dose-dependent associations.
Se and SELENOP declined during pregnancy. There were dose-dependent inverse associations of early GPX3 with late pregnancy GDM (WHO 2013), fasting glucose, insulin, HOMA-IR, and 2 h glucose. The odds ratio (OR) of GDM was 0.33 (95% CI: 0.16, 0.65) for 1 log-scale-increment in early GPX3 activity. Late pregnancy GPX3 and SELENOP were inversely associated with GDM and HOMA-IR; the OR of GDM was 0.21 (95% CI: 0.12, 0.38) and 0.52 (95% CI: 0.35, 0.77), for 1 log-scale-increment of GPX3 and SELENOP, respectively. A decline in Se biomarkers during pregnancy was associated with a higher risk of GDM and higher HOMA-IR. Low GPX3 activity in late pregnancy was associated with a higher risk of large for gestational-age offspring, partly (∼20%) mediated by fasting glucose concentrations (P = 0.006).
Low serum Se in pregnancy, particularly GPX3 activity, is independently associated with risk of GDM and large for gestational age. Offering Se status assessment in pregnancy identifies females at high risk for GDM who may benefit from Se substitution.
Effect of co-encapsulation of Lactobacillus acidophilus LA5 and selenium in hydrogelated matrix of basil seed mucilage/sodium caseinate on properties of set yogurt
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This study aims to prepare and optimize basil seed mucilage and sodium caseinate as a biocomposite wall to co-encapsulate Lactobacillus acidophilus LA5 and selenium. The efficacy of this biocomposite wall in improving the viability of L. acidophilus LA5 under in vitro acidic conditions was investigated. The mixture design method was applied to find optimal ratio of basil seed mucilage/sodium caseinate as components of the capsule wall. The maximum encapsulation efficiency of the selenium and L. acidophilus LA5 and the minimum zeta potential led to the selection of the optimal ratio of basil seed mucilage/sodium caseinate (basil seed mucilage 58.27% and sodium caseinate 41.73%). Possible cross-linking of basil seed mucilage and sodium caseinate, thermal properties, crystal structure, and morphology of the capsule were investigated using FTIR, DSC, XRD, and SEM tests, respectively. The composite wall of basil seed mucilage/sodium caseinate significantly enhanced the viability of encapsulated L. acidophilus LA5 in comparison to the control sample (free L. acidophilus LA5) (p < 0.05). Five yogurt samples were produced, including samples with free probiotic, free probiotic bacterium and selenium, free selenium, control (no probiotic bacterium and selenium), and probiotic yogurt with encapsulated selenium and probiotic bacterium. The physical, chemical, sensorial, and microbial characteristics of yogurt samples were investigated during storage for 21 days at 4 °C. Yoghurt enriched with free selenium and microcapsules (co-encapsulated probiotic and selenium) had minimum and maximum viscosities, respectively (p < 0.05). In addition, the probiotic yogurt sample with encapsulated L. acidophilus LA5 and selenium received a higher overall acceptance score than the other treatments (p < 0.05). As a result, basil seed mucilage and sodium caseinate based composite wall was demonstrated great potential to encapsulate probiotics and selenium for application in yogurt formulation.
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Despite having the highest number of preterm births globally, no genomic study on preterm birth was previously published from India or other South-Asian countries.
We conducted a genome-wide association (GWA) study of spontaneous preterm birth (sPTB) on 6211 women from India. We used a novel resampling procedure to identify the associated single nucleotide polymorphisms (SNPs) followed by haplotype association analysis and imputation.
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Department of Biotechnology (India), Grand Challenges India - All Children Thriving Program and Biotechnology Industry Research Assistance Council (BIRAC).
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: Part of the work cited in this manuscript was supported by Tommy's Charity (registered charity 1060508) as is H.D.M. and The Biotechnology and Biological Sciences Research Council (Biotechnology and Biological Sciences Research Council, United Kingdom).

: The authors report no conflict of interest.

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Expert reviewObstetricsSelenium in reproductive health

Section snippets

Selenium, amino acids, and selenoproteins

Dietary selenium

Selenium deficiency

Selenium toxicity

Male fertility

Selenium and normal pregnancy

Miscarriage

Conclusions

The two faces of selenium

J Nutr

Selenium: an essential element for immune function

Immunol Today

Selenium as an integral part of factor 3 against dietary necrotic liver degeneration

J Am Chem Soc

Selenium in food and health

Molecular biology of selenoproteins

Annu Rev Nutr

Lessons from basic research in selenium and cancer prevention

J Nutr

Metabolic balance of zinc, copper, cadmium, iron, molybdenum and selenium in young New Zealand women

Br J Nutr

Urinary and fecal excretions and absorption of a large supplement of selenium: superiority of selenate over selenite

Am J Clin Nutr

The renal excretion of selenium

Biol Trace Elem Res

Selenium

Content of non-mercury-associated selenium in human tissues

Biol Trace Elem Res

Selenium, the thyroid, and the endocrine system

Endocr Rev

Characterization of mammalian selenoproteomes

Science

Selenium and endocrine systems

J Endocrinol

Assessment of requirements for selenium and adequacy of selenium status: a review

Eur J Clin Nutr

Selenium: biochemical role as a component of glutathione peroxidase

Science

Selenium-dependent enzymes in endothelial cell function

Antioxid Redox Signal

The importance of selenium to human health

Lancet

Selenium in global food systems

Br J Nutr

Nutriprevention of disease with high-selenium wheat

J Australas Coll Nutr & Environ Med

Selenium in diet, blood, and toenails in relation to human health in a seleniferous area

Am J Clin Nutr

Dietary intake of selenium

Vegetarians and vegans may be most at risk from low selenium intakes

BMJ

Indexes of selenium status in human populations

Am J Clin Nutr

Selenium

Selenium and iodine supplementation of rural Tibetan children affected by Kashin-Beck osteoarthropathy

Am J Clin Nutr

Interacting nutritional and infectious etiologies of Keshan diseaseInsights from Coxsackie virus B-induced myocarditis in mice deficient in selenium or vitamin E

Biol Trace Elem Res

Selenium deficiency and viral infection

J Nutr

Selenium supplementation of Chinese women with habitually low selenium intake increases plasma selenium, plasma glutathione peroxidase activity, and milk selenium, but not milk glutathione peroxidase activity

J Nutr Biochem

Food-chain selenium and human health: emphasis on intake

Br J Nutr

Selenium in self-selected diets of Maryland residents

J Am Diet Assoc

Estimation of antioxidant intakes from diet and supplements in US adults

J Nutr

Selenium content of food consumed by Canadians

J Nutr

Effects of selenium supplementation of food crops

Adaptive dysfunction of selenoproteins from the perspective of the triage theory: why modest selenium deficiency may increase risk of diseases of aging

FASEB J

National Diet and Nutrition Survey

Marginal dietary selenium intakes in the UK: are there functional consequences?

J Nutr

Selenium toxicity in cattle in CoMeath

Ir Vet J

Expert review
Obstetrics
Selenium in reproductive health