Role of sulphate in development

Abstract

Sulphate contributes to numerous processes in mammalian physiology, particularly during development. Sulphotransferases mediate the sulphate conjugation (sulphonation) of numerous compounds, including steroids, glycosaminoglycans, proteins, neurotransmitters and xenobiotics, transforming their biological activities. Importantly, the ratio of sulphonated to unconjugated molecules plays a significant physiological role in many of the molecular events that regulate mammalian growth and development. In humans, the fetus is unable to generate its own sulphate and therefore relies on sulphate being supplied from maternal circulation via the placenta. To meet the gestational needs of the growing fetus, maternal blood sulphate concentrations double from mid-gestation. Maternal hyposulphataemia has been linked to fetal sulphate deficiency and late gestational fetal loss in mice. Disorders of sulphonation have also been linked to a number of developmental disorders in humans, including skeletal dysplasias and premature adrenarche. While recognised as an important nutrient in mammalian physiology, sulphate is largely unappreciated in clinical settings. In part, this may be due to technical challenges in measuring sulphate with standard pathology equipment and hence the limited findings of perturbed sulphate homoeostasis affecting human health. This review article is aimed at highlighting the importance of sulphate in mammalian development, with basic science research being translated through animal models and linkage to human disorders.Reproduction (2013) 146 R81-R89

Placental control of drug delivery

“…In terms of physiological functions, this enzyme may be involved in the sulfation of dehydroepiandrosterone in the placenta [128]. Cholesterol sulfate is also synthesized in the placenta [130]. Sulfation of hormones can occur by SULT1A1 and SULT1A3 activity, though SULT1E1 (also known as estrogen sulfotransferase) functions in the placenta as well [129].…”

Loss of the sulfate transporter Slc13a4 in placenta causes severe fetal abnormalities and death in mice

“…In addition, sulfonation of glycosaminoglycans is important for development of some tissues, as several growth factor gradients and ligand-receptor interactions are dependent on these sulfonated extracellular constituents [3]. Not surprisingly therefore, reduced sulfonation capacity has been linked to disorders of skeletal, eye, vascular and craniofacial development, demonstrating a critical requirement for sulfate in these tissues [4]. Despite a fundamental role for sulfate during development, the fetus appears to have a limited capacity to generate sulfate from sulfur-containing amino acids, and is thought to be reliant on maternal sulfate provision [5].…”

A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder

“…M aintaining the required biological ratio of sulfated versus non-sulfated molecules in the cell is critical for several biological processes ranging from fetal development and hormone metabolism to growth factor signalling, bone remodelling and degradation of macromolecules [1][2][3][4][5] . Thus, sulfate homeostasis is highly dynamic and tightly regulated by multiple enzymes including a large family of sulfatase enzymes that hydrolyse sulfate esters from many substrates, including sulfolipids, steroid sulfates and glycosaminoglycans (GAGs) 6 .…”

“…Sulfation represents an important protein modification, with diverse roles in several biological settings [1][2][3] . Importantly, sulfate metabolism is highly dynamic and sulfate groups are efficiently removed from sulfated proteins by a large family of sulfatase enzymes 7 .…”