Abstract Title:

Roundup Disrupted Male Reproductive Functions By Triggering Calcium-Mediated Cell Death In Rat Testis And Sertoli Cells.

Abstract Source:

Free Radic Biol Med. 2013 Jun 29. Epub 2013 Jun 29. PMID: 23820267

Abstract Author(s):

Vera Lúcia de Liz Oliveira Cavalli, Daiane Cattani, Carla Elise Heinz Rieg, Paula Pierozan, Leila Zanatta, Eduardo Benedetti Parisotto, Danilo Wilhelm Filho, Fátima Regina Mena Barreto Silva, Regina Pessoa-Pureur, Ariane Zamoner

Article Affiliation:

Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis-Santa Catarina, Brazil.


Glyphosate is the primary active constituent of the commercial pesticide Roundup®. The present results show that acute Roundup® exposure at low doses (36ppm, 0.036g/L) for 30min induces oxidative stress and activates multiple stress-response pathways leading to Sertoli cell death in prepubertal rat testis. The pesticide increased intracellular Ca(2+) concentration by openingL-type voltage-dependent Ca(2+) channels (L-VDCC) as well as endoplasmic reticulum IP3 and ryanodine receptors, leading to Ca(2+) overload within the cells, which set off oxidative stress and necrotic cell death. Similarly, 30min incubation of testis with glyphosate alone (36ppm) also increased (45)Ca(2+) uptake. These events have been prevented by the antioxidants Trolox® and ascorbic acid. Activated protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K) and the mitogen-activated protein kinases (MAPKs), such as ERK1/2 and p38MAPK have played a role in eliciting Ca(2+) influx and celldeath. Roundup® decreased the levels of reduced glutathione (GSH) and increased the amounts of thiobarbituric reactive species (TBARS) and protein carbonyls. Also, exposure to the glyphosate-Roundup® has stimulated the activity of glutathione peroxidase, glutathione reductase, glutathione-S-transferase, gamma-glutamyl transferase (γGT), catalase, superoxide dismutase and glucose-6-phosphate dehydrogenase, supporting downregulated GSH levels. Glyphosate has been described as an endocrine disruptor affecting the male reproductive system; however, the molecular basis of its toxicity remains tobe clarified. We could propose that Roundup® toxicity, implicating in Ca(2+) overload, cell signaling misregulation, stress response of the endoplasmic reticulum and/or depleted antioxidant defenses could contribute to Sertoli cell disruption of spermatogenesis that could impact male fertility.

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