Implications of glyphosate-based herbicides on the female reproductive system and reproductive outcomes

Background Glyphosate-based herbicides (GBHs) are the most widely used herbicides in the United States, accounting for 19% of estimated global use. Although the Environmental Protection Agency has reaffirmed that the active ingredient glyphosate (GLY) is safe for humans, recent studies on exposure have suggested an association with cancer, metabolic disorders, endocrine disruption and infertility, and Alzheimer’s and Parkinson’s disease. Recently, we have shown that GLY exposure deteriorates metaphase II oocyte quality through zinc deficiency, ROS accumulation, and chromosome disruption. In this work, we review the mechanisms of GLY toxicity in the female reproductive tract and discuss the potential clinical implications of GLY exposure on female reproductive health. Methods PubMed was searched using the keywords “glyphosate,” “glyphosate-based herbicides,” “reproductive toxicity,” “reproductive function,” “ovarian function,” “female infertility,” “endocrine disruptors,” and “oxidative stress” up to March 2024. Results Exposure to GLY is associated with adverse reproductive effects in all animal models and cell lines studied. GLY adversely affects the female reproductive tract through increased ROS generation, Zn deficiency, hormonal imbalances, aromatase inhibition, alterations in uterine morphology, and diminished oocyte quality and ovarian function. Collectively, the effects of GLY exposure on reproductive and endocrine function may increase the risk of female reproductive diseases, including PCOS, endometriosis, infertility, and miscarriage. Conclusions The ongoing debate about the effects of GLY exposure increasingly exemplifies the public health issue surrounding its consequences on female reproductive health, fertility, and epigenetics. Thus, increased research efforts are warranted regarding the safety and efficacy of GBH on female reproduction.