The Effects of Perchlorate on Thyroidal Gene Expression are Different from the Effects of Iodide Deficiency

Abstract

Perchlorate (ClO₄⁻), which is a ubiquitous and persistent ion, competitively interferes with iodide (I) accumulation in the thyroid, producing I deficiency (ID), which may result in reduced thyroid hormone synthesis and secretion. Human studies suggest that ClO₄⁻ presents little risk in healthy individuals; however, the precautionary principle demands that the sensitive populations of ID adults and mothers require extra consideration. In an attempt to determine whether the effects on gene expression were similar, the thyroidal effects of ClO₄⁻ (10 mg/kg) treatment for 14 d in drinking water were compared with those produced by 8 wk of ID in rats. The thyroids were collected (n = 3 each group) and total mRNA was analyzed using the Affymetrix Rat Genome 230 2.0 GeneChip. Changes in gene expression were compared with appropriate control groups. The twofold gene changes due to ID were compared with alterations due to ClO₄⁻ treatment. One hundred and eighty-nine transcripts were changed by the ID diet and 722 transcripts were altered by the ClO₄⁻ treatment. Thirty-four percent of the transcripts changed by the I-deficient diet were also altered by ClO₄⁻ and generally in the same direction. Three specific transporter genes, AQP1, NIS, and SLC22A3, were changed by both treatments, indicating that the membrane-specific changes were similar. Iodide deficiency primarily produced alterations in retinol and calcium signaling pathways and ClO₄⁻ primarily produced changes related to the accumulation of extracellular matrix proteins. This study provides evidence that ClO₄⁻, at least at this dose level, changes more genes and alters different genes compared to ID.

Developmental timing of perchlorate exposure alters threespine stickleback dermal bone

“…Given that the embryo’s source of T4 and T3 is maternal at this early stage of development (Power et al, 2001), and the expression of NIS and formation of functioning thyroid follicles begins sometime between 8 and 11 dpf (A. Petersen, J. Postlethwait, W. A. Cresko, C. L. Buck and F. A. von Hippel, unpublished data), hypothyroidism via perchlorate is likely not driving these effects. Perchlorate may alter the timing and/or rate of development of some traits through non-thyroidal pathways as has been demonstrated in gene expression studies (McDougal et al, 2011). NIS is present in non-thyroidal tissues of vertebrates, such as mammary glands, the gastric mucosa, salivary glands and kidneys (Josefsson et al, 2002).…”

“…Individuals most at risk to the effects of perchlorate exposure are iodide deficient, and/or in early development or metamorphosis (Carr and Patiño, 2011; Leung et al, 2010; Liu and Chan, 2002; Melse-Boonstra and Jaiswal, 2010; Tietge et al, 2005; Trumbo, 2010). In addition, perchlorate may have effects independent of iodide deficiency (LaRoche et al, 1966; McDougal et al, 2011). Environmental exposure in fish occurs via the respiratory and gastrointestinal epithelia, integument, and sometimes ingested food (Furin et al, 2013).…”

Perchlorate disrupts embryonic androgen synthesis and reproductive development in threespine stickleback without changing whole-body levels of thyroid hormone

“…Thus, more of the exposed thyrocyte surface may be lined with NIS, increasing the potential for overcoming the interruption to iodide transport caused by perchlorate. Supporting this idea is the finding that the human NIS gene is expressed in thyroid follicular cells, and NIS gene expression in mammals is upregulated at low doses of perchlorate (McDougal et al, 2011). Furthermore, previous studies found that the iodide-concentrating function is compromised at perchlorate doses that do not affect circulating thyroid hormone levels (Lawrence et al, 2005), suggesting that NIS function is highly sensitive to perchlorate and that compensatory mechanism can adjust for perchlorate toxicity.…”

Syntheses, structures and anion exchange properties of accommodative silver chains using a positively charged and flexible ligand

“…In particular, many oxohydroxo anionic forms of p-block elements and metals, like perchlorate (ClO 4 − ) [34], sulfate (SO 4 2− ), and chromate (CrO 4 2− ), are listed as major pollutants, because these anions can adversely affect human health and are toxic, mutagenic, and are considered as human carcinogens [35][36][37]. Traditionally, ion exchange resin is the most common material, and has been widely exploited.…”