Role for Selenium in Metabolic Homeostasis and Human Reproduction

Abstract

Selenium (Se) is a micronutrient essential for life. Dietary intake of Se within the physiological range is critical for human health and reproductive functions. Selenium levels outside the recommended range have been implicated in infertility and variety of other human diseases. However, presently it is not clear how different dietary Se sources are processed in our bodies, and in which form or how much dietary Se is optimum to maintain metabolic homeostasis and boost reproductive health. This uncertainty leads to imprecision in published dietary guidelines and advice for human daily intake of Se and in some cases generating controversies and even adverse outcomes including mortality. The chief aim for this review is to describe the sources of organic and inorganic Se, the metabolic pathways of selenoproteins synthesis, and the critical role of selenprotenis in the thyroid gland homeostasis and reproductive/fertility functions. Controversies on the use of Se in clinical practice and future directions to address these challenges are also described and discussed herein.

Keywords: body metabolism; fertility; hormones; obesity; selenium; selenoproteins; thyroid.

Figure 1

Schematic representation of the known metabolic pathways contributing to selenoprotein biosynthesis [52] (Created with BioRender.com (2021)). Pathways include (a) Aminoacylation of Selenocysteine–tRNA[Ser]Sec, (b) Chemical reduction of selenite into selenide by either the thioredoxin/thioredoxin reductase (TXN/TXNRD) system or of the glutathione peroxidase redox (GSH/GR) system (c) Catalyzation of selenomethionine-derived selenocysteine by three enzymes: cystathionine ß-synthase, cystathionine ß-lyase and selenocysteine ß-lyase (SCL) (d) Demethylation reaction of methylselenol (CH₃Se) catalyzed by methylselenol demethylase. Abbreviations includes: (SPS2) selenophosphate 2 synthetase 2, (SerRS) seryl-tRNA synthetase, (PSKT) phosphoseryl-tRNA kinase, (SepSecS) Sec synthase, (TMSe) trimethylselenonium ion.

Figure 2

(A) Gross and microanatomy of thyroid gland. (B) Synthesis of thyroid hormones and role of selenoproteins in colloid of thyroid ( Adapted from “Thyroid Gland Anatomy and Histology”, by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates, accessed on 13 April 2021) and is adapted from [71]. (1) Thyroglobulin synthesis: thyroglobulin, the building block of thyroid hormone is synthesized in the endoplasmic reticulum of follicular cells; (2) Iodination: iodine then combines with thyroglobulin, forming iodinated thyroglobulin after a series of iodination processes; (3) Proteolysis: the iodinated thyroglobulin is broken down into T4 (~90%) and T3 (~10%) hormones; (4) T3 and T4 production: Both T3 and T4 then travel in blood and reach different tissues, where T4 is further broken down to the active T3 in local tissues, primarily in the liver to regulate fat and carbohydrate metabolism, thermogenesis, growth, and development [72].

Figure 3

Selenium-mediated balance and imbalance in the thyroid and reproductive functions (Created with BioRender.com, accessed on 2021).