Glyphosate Herbicide: Reproductive Outcomes and Multigenerational Effects

Abstract

Glyphosate base herbicides (GBHs) are the most widely applied pesticides in the world and are mainly used in association with GBH-tolerant crop varieties. Indiscriminate and negligent use of GBHs has promoted the emergence of glyphosate resistant weeds, and consequently the rise in the use of these herbicides. Glyphosate, the active ingredient of all GBHs, is combined with other chemicals known as co-formulants that enhance the herbicide action. Nowadays, the safety of glyphosate and its formulations remain to be a controversial issue, as evidence is not conclusive whether the adverse effects are caused by GBH or glyphosate, and little is known about the contribution of co-formulants to the toxicity of herbicides. Currently, alarmingly increased levels of glyphosate have been detected in different environmental matrixes and in foodstuff, becoming an issue of social concern. Some in vitro and in vivo studies have shown that glyphosate and its formulations exhibit estrogen-like properties, and growing evidence has indicated they may disrupt normal endocrine function, with adverse consequences for reproductive health. Moreover, multigenerational effects have been reported and epigenetic mechanisms have been proved to be involved in the alterations induced by the herbicide. In this review, we provide an overview of: i) the routes and levels of human exposure to GBHs, ii) the potential estrogenic effects of glyphosate and GBHs in cell culture and animal models, iii) their long-term effects on female fertility and mechanisms of action, and iv) the consequences on health of successive generations.

Keywords: adverse reproductive outcomes; estrogenic effects; female fertility; glyphosate; glyphosate-based herbicides; implantation failures; maternal exposure; multigenerational effects.

Figure 1

The scheme summarizes the multigenerational effects of the herbicide glyphosate (active ingredient and a glyphosate-based herbicide) on F1 adult female rats and their F2 offspring after perinatal exposure (during gestation and lactation) through food. The color green or red of the arrows denotes induction or inhibition of the molecular targets, respectively. Gly, glyphosate (active ingredient); GBH, glyphosate-based herbicide; E2, 17β-estradiol; ERα, estrogen receptor alpha; Lif, Leukemia inhibitory factor; Hoxa10, Homeobox A10.