Effects of Alpha-Lipoic Acid on Glyphosate-Treated Human Granulosa Cells: A Cross-Sectional Study

An association between Glyphosate (GLY) exposure and a higher frequency of miscarriage and preterm birth has been shown. To evaluate the effects of alpha-lipoic acid (ALA) on folliculogenesis gene expression and oxidative stress in human GLY-treated granulosa cells (GCs).

GCs were obtained from 46 healthy women who had tubal or male infertility factors. The GCs were cultured and treated with GLY (250 μg mL^-1), ALA (50 μg mL^{- 1}), or 250 GLY + 50 ALA for 24 h. The effect of ALA on apoptosis was evaluated using DAPI staining and flow cytometry.We assessed the expression of several genes in treated GCs using real-time PCR. We looked at the Forkhead box protein O1 (FOXO1), NADPH oxidase 4 (NOX4), Vanin-1 (VNN1), and steroidogenic acute regulatory protein (StAR) genes. Additionally, we examined antioxidant genes, including glutathione peroxidase (GPX), catalase (CAT), and superoxide dismutase (SOD).

DNA fragmentation was less pronounced in the ALA-treated and GLY + ALA groups compared to the GLY-treated group. ALA treatment reduced the apoptotic ratio in GLY treatment and the combination of GLY + ALA (5.5% and 19.6% vs. 35.8%), respectively. GLY reduced the fold expression of CAT, GPX, and SOD by 0.27, 0.24, and 0.44, respectively. In the ALA treatment group, the fold expression of SOD, CAT, and GPX exceeded that in the untreated group (1.2, 1.02, and 1.7, respectively). GLY decreased the expression of the VNN1 and StAR genes while increasing the expression of the FOXO1 and NOX4 genes compared to the control group. Furthermore, ALA decreased FOXO1 and NOX4 expression in GCs and increased VNN1 and StAR gene expression.

Exposure to GLY induced apoptosis, and ALA increased the expression of antioxidant genes in GCs. Additionally, ALA can be recommended to reduce the damage caused by oxidants to the female reproductive system.