Dietary Glyphosate Exposure Disrupts Hepatic and Reproductive Function in Female Zebrafish at Regulatory Safe Levels

Area of Science:

• Environmental Toxicology
• Reproductive Biology
• Endocrinology

Background:

• Glyphosate (GLY) is a widely used herbicide.
• Evidence suggests GLY can impair animal endocrine and reproductive functions.
• Regulatory assessment of GLY effects at approved doses is crucial due to its persistence.

Purpose of the Study:

• To investigate the effects of dietary glyphosate on the hepato-gonadal axis in adult female zebrafish.
• To assess reproductive and endocrine disruptions at regulatory-approved and higher doses.
• To evaluate GLY's impact on oocyte maturation, fertilization, and embryo development.

Main Methods:

• Adult female zebrafish were fed diets containing GLY at 0.5 mg/kg/day (ADI), 5 mg/kg/day, and 50 mg/kg/day (NOAEL) for 21 days.
• Measurements included cortisol, cortisone, hepatic glycogen, ferroptosis markers, gene expression related to oogenesis and estrogen signaling, fertilization rates, and embryo mortality.
• Histological examination of follicles was also performed.

Main Results:

• Dietary GLY induced dose-dependent disruptions in the hepato-gonadal axis.
• High GLY doses caused chronic stress, hepatic glycogen accumulation, and ferroptotic stress.
• Gene expression alterations related to oocyte maturation and estrogen signaling were observed, leading to reduced fertilization and compromised gamete quality.
• Even the lowest dose affected oogenesis genes, while GLY5 increased embryo mortality.

Conclusions:

• Dietary glyphosate disrupts hepatic metabolism, endocrine signaling, and reproduction in a non-monotonic manner in female zebrafish.
• These effects occurred at levels considered safe by EFSA, highlighting potential risks.
• Current safety thresholds for glyphosate may need reevaluation, particularly concerning female-specific reproductive risks.