Chronic Exposure to Glyphosate-Based Herbicides Compromises Semen Quality, Which in Turn Disrupts the Immunoregulation of the Female Genital Tract and Affects Fetal Development

Maria Sol Martinez – Centro de Investigación en Bioquímica Clínica e Inmunología (Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Córdoba); Fernando Nicolas Ferreyra – Centro de Investigación en Bioquímica Clínica e Inmunología (Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Córdoba); Yamila Fariz – Centro de Investigación en Bioquímica Clínica e Inmunología (Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Córdoba); Daniela Andrea Paira – Centro de Investigación en Bioquímica Clínica e Inmunología (Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Córdoba); Carolina Olivera – Centro de Investigación en Bioquímica Clínica e Inmunología (Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Córdoba); Andrea Tissera – Laboratorio de Andrología y Reproducción (Córdoba - Argentina); Rosa Molina – Laboratorio de Andrología y Reproducción (Córdoba - Argentina); Virginia Elena Rivero – Centro de Investigación en Bioquímica Clínica e Inmunología (Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Córdoba); Ruben Dario Motrich – Centro de Investigación en Bioquímica Clínica e Inmunología (Consejo Nacional de Investigaciones Científicas y Técnicas - Universidad Nacional de Córdoba)

Abstract Text: The widespread use of glyphosate-based herbicides (GBH) has raised significant concerns about their potential impact on reproductive health. However, most available data remain controversial, leaving a significant gap in understanding GBH's specific effects on male fertility in humans.
This study aimed to evaluate sperm quality and semen inflammation in men chronically exposed to GBH. Additionally, an animal model was used to investigate GBH’s effects on male fertility as well as embryonic and placental development.
Sperm quality in human patients was analyzed following WHO guidelines. Semen levels of cytokines and leukocyte subsets were quantitated by flow cytometry. In parallel, male C57BL/6 mice were orally treated with GBH or water for 35 days. Males were then mated with BALB/c females. Sperm quality, different fertility parameters, and placental development were analyzed. Moreover, uterine immune cell infiltration was evaluated at the peri-implantation window.
Men exposed to GBH exhibited reduced sperm concentration, motility, morphology and significant semen inflammation characterized by increased levels of leukocytes and cytokines. Similarly, GBH-exposed mice showed reduced sperm quality. Interestingly, females mated with these males showed significant uterine inflammation during the peri-implantation window, evidenced by increased infiltration of macrophages and CD4 and CD8 T lymphocytes. Strikingly, pups sired by GBH-exposed males showed altered embryonic and placental development, with reduced fetal and placental sizes.
These findings indicate that chronic exposure to GBH adversely affects semen quality, which in turn hinders the sperm's ability to physiologically induce immunoregulation in the female genital tract. This impairment also negatively impacts placental and fetal development.