The association between urinary glyphosate metabolites and biomarkers of oxidative stress among pregnant women in PROTECT birth cohort study

Abstract

Background: Glyphosate is a widely used herbicide in the global agriculture industry. Glyphosate and its primary metabolite, aminomethyl phosphonic acid (AMPA), have been shown to disrupt endocrine function and induce oxidative stress within in vitro and animal studies. To our knowledge, these relationships have not been previously characterized in epidemiological settings. Elevated urinary levels of glyphosate and AMPA may impact the health of vulnerable populations such as pregnant women via multiple mechanisms including oxidative stress. Methods: Glyphosate and AMPA were measured in 347 urine samples collected at multiple visits from pregnant women in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) birth cohort. Urinary biomarkers of oxidative stress, comprising 8-isoprostane-prostaglandin-F2a (8-iso-PGF2a), its main metabolite 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (8-iso-PGF2a metabolite) and prostaglandin-F2a (PGF2a), were also measured. One-way ANOVA tests evaluated differences in exposure and oxidative stress biomarker concentrations between study visits. Linear mixed effect models assessed the association between exposures and oxidative stress adjusting for maternal age, smoking status, alcohol consumption, household income and specific gravity. Results: No significant differences in exposure or oxidative stress biomarker concentrations were observed between study visits. An interquartile range (IQR) increase in AMPA was associated with 9.5% (95% CI: 0.5%-19.3%) higher 8-iso-PGF2a metabolite. Compared to the lowest exposure group, the second and third tertiles of AMPA were significantly associated with 12.8% (0.6%-26.5%) and 15.2% (1.8%-30.3%) higher 8-iso-PGF2a metabolite, respectively. An IQR increase in glyphosate was suggestively associated with 4.7% (-0.9%-10.7%) higher 8-iso-PGF2a. Conclusions: Urinary concentrations of the main metabolite of glyphosate, AMPA, were associated with higher levels of certain oxidative stress biomarkers. Associations with glyphosate reflected similar trends, although findings were not as strong. Additional research is required to better characterize the association between glyphosate exposure and biomarkers of oxidative stress, as well as potential downstream health consequences.