Alteration of estrogen-regulated gene expression in human cells induced by the agricultural and horticultural herbicide glyphosate

Abstract

<jats:p> Gene expression is altered in mammalian cells (MCF-7 cells), by exposure to a variety of chemicals that mimic steroid hormones or interact with endocrine receptors or their co-factors. Among those populations chronically exposed to these endocrine disruptive chemicals are persons, and their families, who are employed in agriculture or horticulture, or who use agricultural/horticultural chemicals. Among the chemicals most commonly used, both commercially and in the home, is the herbicide glyphosate. Although glyphosate is commonly considered to be relatively non-toxic, we utilized in vitro DNA microarray analysis of this chemical to evaluate its capacity to alter the expression of a variety of genes in human cells. We selected a group of genes, determined by DNA microarray analysis to be dysregulated, and used quantitative real-time PCR to corroborate their altered states of expression. We discussed the reported function of those genes, with emphasis on altered physiological states that are capable of initiating adverse health effects that might be anticipated if gene expression were significantly altered in either adults or embryos exposed in utero. Human &amp; Experimental Toxicology (2007) 26, 747— 752 </jats:p>

Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide

“…Glyphosate has been suggested to act as an estrogen agonist based on assays in cultures of human breast cancer cells at comparable concentrations to the native hormone3738. Other studies, albeit at much higher doses, have also shown that glyphosate can uncouple liver mitochondrial oxidative phosphorylation10.…”

Potential toxic effects of glyphosate and its commercial formulations below regulatory limits

“…However, the reproducibility and the relevance for in vivo situations need to be confirmed by other studies. Alterations of estrogenic gene expression have also been demonstrated in another study investigating transcriptome responses of mammary cells to a GlyBH at higher levels (Hokanson et al, 2007). In another study, glyphosate and Roundup induced similar proliferative effects on MCF-7 mammary cells in both normal and charcoal-dextran-treated fetal bovine serum, suggesting a non-estrogenic mechanism of proliferation (Lin and Garry, 2000).…”

“…Finally, it inhibits testosterone synthesis both in vitro on fresh adult rat isolated testicular cells (Clair et al, 2012) and in vivo in rats (Romano et al, 2010) from 5 mg/kg bw/d, it also disrupted testicular aromatase mRNA levels, among other markers (Cassault-Meyer et al, 2014). In a transcriptomic study in MCF7 mammary human cells, a GlyBH altered estrogen-regulated gene expressions and intracellular responses to hypoxia from 2.3 ppm glyphosate (Hokanson et al, 2007). It also inhibits the transcriptional activities of both androgen and estrogen receptors (Gasnier et al, 2009) from 0.5 mg/L Roundup (containing 0.2 mg/L G).…”

“…Consequently, the described effects in literature vary widely. In fact, not all authors clearly indicate which GlyBH they have used (Chan et al, 2007;Hokanson et al, 2007;Sivikova and Dianovsky, 2006), confusing the products or the adjuvants (Contardo-Jara et al, 2009;Gehin et al, 2005). For instance, not all adjuvant mixtures contain POEA.…”

Estimating maternal and prenatal exposure to glyphosate in the community setting

“…EPA, 1993). Regulatory studies show that glyphosate per se is practically harmless to humans, wildlife and the environment; however, recent research indicates other ingredients in the formulation increase the toxicity and availability of glyphosate in mammalian (including human) cells, tissues and organs, raising concerns about the safety of glyphosate (Axelrad et al, 2003;Benachour and Séralini, 2009;Dallegrave et al, 2007;Hokanson et al, 2007;Richard et al, 2005).…”