A glyphosate-based herbicide induces necrosis and apoptosis in mature rat testicular cells in vitro, and testosterone decrease at lower levels

Toxicol In Vitro. 2012 Mar;26(2):269-79. doi: 10.1016/j.tiv.2011.12.009. Epub 2011 Dec 19.

Abstract

The major herbicide used worldwide, Roundup, is a glyphosate-based pesticide with adjuvants. Glyphosate, its active ingredient in plants and its main metabolite (AMPA) are among the first contaminants of surface waters. Roundup is being used increasingly in particular on genetically modified plants grown for food and feed that contain its residues. Here we tested glyphosate and its formulation on mature rat fresh testicular cells from 1 to 10000ppm, thus from the range in some human urine and in environment to agricultural levels. We show that from 1 to 48h of Roundup exposure Leydig cells are damaged. Within 24-48h this formulation is also toxic on the other cells, mainly by necrosis, by contrast to glyphosate alone which is essentially toxic on Sertoli cells. Later, it also induces apoptosis at higher doses in germ cells and in Sertoli/germ cells co-cultures. At lower non toxic concentrations of Roundup and glyphosate (1ppm), the main endocrine disruption is a testosterone decrease by 35%. The pesticide has thus an endocrine impact at very low environmental doses, but only a high contamination appears to provoke an acute rat testicular toxicity. This does not anticipate the chronic toxicity which is insufficiently tested, and only with glyphosate in regulatory tests.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / metabolism
  • Adenylate Kinase / metabolism
  • Animals
  • Apoptosis / drug effects
  • Aromatase / genetics
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cells, Cultured
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor beta / genetics
  • Germ Cells / drug effects*
  • Germ Cells / metabolism
  • Glycine / analogs & derivatives*
  • Glycine / toxicity
  • Herbicides / toxicity*
  • Leydig Cells / drug effects*
  • Leydig Cells / metabolism
  • Male
  • Necrosis / chemically induced
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Androgen / genetics
  • Sertoli Cells / drug effects*
  • Sertoli Cells / metabolism
  • Testosterone / metabolism

Substances

  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Herbicides
  • RNA, Messenger
  • Receptors, Androgen
  • Testosterone
  • glyphosate
  • 3-Hydroxysteroid Dehydrogenases
  • Aromatase
  • Adenylate Kinase
  • Caspase 3
  • Caspase 7
  • Glycine