ORIGINAL ABSTRACT

Background: Exposure to anthropogenic and/or natural (e.g., herbicides or mycotoxins) endocrine-disrupting chemicals (EDCs) has been linked to several reproductive disorders. Glyphosate (GLY), a common agricultural agent, is a potential element of the exposome that bioaccumulates and has potential endocrine and oxidative stress-related effects. However, data on its presence in the human ovarian microenvironment remain limited. Our study examined GLY levels in follicular fluid (ff) and serum and their relationships with oxidative stress markers, reproductive hormones, and stress hormones in women undergoing in vitro fertilization (IVF). Methods: 50 women undergoing controlled ovarian stimulation participated. Serum and ff samples were routinely collected during oocyte retrieval. GLY, related hormones (e.g., cortisol, estradiol-E2, anti-Müllerian hormone-AMH, and melatonin-MT), an oxidative stress marker malondialdehyde (MDA), antioxidant enzyme activities, total antioxidant capacity, and co-occurring natural pollutant mycotoxin levels were measured. Relationships between GLY levels and these mediators were assessed using correlation and regression analyses. Results: GLY was detected in both serum and ff at similar concentrations (0.038 ± 0.006 ng/mL vs. 0.045 ± 0.006 ng/mL; p = 0.414). Follicular GLY levels showed a positive association with MDA (Spearman's r = 0.4487, p < 0.001), explaining 28.6% of the variability in follicular MDA. Serum GLY was positively associated with serum (β = 40.26, p = 0.0058) and follicular E2 (r = 0.29, p = 0.042). Serum GLY levels were negatively correlated with cortisol (β = -0.0188, p = 0.020). A slight correlation between follicular GLY and MT was observed (p = 0.03). No associations were found between GLY levels and age, body mass index, AMH, the recombinant gonadotropin dose used, antioxidant enzyme activities, follicle count, oocyte yield, or embryo viability. Conclusions: This study might be the first to demonstrate the presence of GLY of exposome in human ff, indicating that environmental exposure to GLY may reach the oocyte microenvironment. The correlation with lipid peroxidation suggests GLY could contribute to follicular oxidative stress. The associations with E2 and cortisol point to potential endocrine-disrupting effects. While no direct impact on IVF outcomes was observed, findings suggest low-level exposure to GLY could influence ovarian physiology through specific biochemical mechanisms.