A Glyphosate-Based Formulation but Not Glyphosate Alone Alters Human Placental Integrity

Abstract

Glyphosate (G)-based herbicidal formulations, such as the most commonly used one, Roundup (R), are major pesticides used worldwide on food and feed. Pregnant women may be frequently exposed to R compounds. These are composed of G, which is declared as the active principle, and other products contained in formulations, named formulants, which have been declared as inerts and diluents by the manufacturers. These formulants have, in fact, been demonstrated to be much more toxic than G, in particular to placental and embryonic human cells. In this work, we thus compared the effect of G and a GT+ formulation named R, using placental perfusion ex vivo. R, but not G alone, was demonstrated to alter the placental permeability of a known small model molecule, antipyrine. Similar results were observed for the fetal venous flow rate. The transfer of G alone increases with time, but is significantly decreased in presence of its formulants. The perfusion of R provokes a destruction of fetal vessels, as demonstrated by immunohistochemistry. Formulants obviously alter the fetal-placental circulation and placental integrity according to time of exposure. Therefore, G does not appear to be the main toxic agent of R. Formulants, although undeclared, include polyoxyethanolamines, PAHs, or heavy metals, and may be responsible for this toxicity. These compounds are also present in other pesticides. The progressive blood flow reduction due to the toxic compounds of formulations may diminish the nutrient supply to the fetus, alter the development, and may enhance the poisoning effects. Although these are preliminary results, they could at least partially explain some adverse pregnancy outcomes in mothers exposed to pesticides or other environmental pollutants. The debate on glyphosate alone is proven insufficient for the understanding of the toxicity.

Review: Mechanisms of Glyphosate and Glyphosate-Based Herbicides Action in Female and Male Fertility in Humans and Animal Models

“…An ex vivo human perfusion system experiment was carried out to analyze whether the placenta is permeable to G (33.8 mg/L). Caffeine and benzoic acid were reported to transfer throughout the perfusion system more easily than G. Only 15% of G crossed the placental barrier to reach the fetal circulation, with a very low permeability coefficient compared with caffein and benzoic acid [81]. Finally, a recent study on placental perfusion ex vivo from human full-term placenta analyzed the difference between G alone (1 ppm) and R formulation containing formulants such as POEA (1 ppm G equivalent) [82].…”

Pesticides in Formulations: New Revolutionary Findings

“…In fact, mass spectrometry analyses of mixtures of pure, usable, commercially available formulations of pesticides revealed hundreds of unidentified compounds spread over Gauss curves [ 4 ], indicating that adjuvants are not only variable and numerous but also contain residual chemicals. More importantly, these make mixtures hundreds to thousands of times more efficient with respect to oxidative stress in vivo and in patients, as demonstrated in court during the Monsanto Affair, or in human placentas [ 6 ] than what is expected from the sole ADI of the purified declared ingredient in the long term that serves as basic data. This insufficiency in assessing chronic effects was confirmed by detailed omics studies in vivo [ 7 , 8 ].…”

Glyphosate‐based herbicide induces long‐lasting impairment in neuronal and glial differentiation

“…[11][12] Several studies have indicated that GLY can reach the developing embryo, inducing toxic effects, since is able to diffuse through the placenta. [23][24][30][31][32] In agreement, GLY exposure in rats, during perinatal phases, results in neurobehavioral, estrogenic, and thyroid hormone alterations in offspring. [33][34][35][36] Considering the extensive use of GBH, it is relevant to evaluate the effect of formulations, particularly when the exposure occurs during development.…”

“…Several studies have indicated that GLY can reach the developing embryo, inducing toxic effects, since is able to diffuse through the placenta 23–24,30–32 . In agreement, GLY exposure in rats, during perinatal phases, results in neurobehavioral, estrogenic, and thyroid hormone alterations in offspring 33–36 .…”