Kafshgiri Sakineh Kaboli, Attaranzadeh Armin, Safarpour Hossein, Ghasemi Fahimeh, Miri-Moghaddam Ebrahim
Royesh Infertility Center Birjand University of Medical Sciences Birjand Iran.
Milad Infertility Center, Imam Reza Hospital Mashhad University of Medical Sciences Mashhad Iran.
Health Sci Rep. 2025 Jun 25;8(6):e70946. doi: 10.1002/hsr2.70946. eCollection 2025 Jun.
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), ALA (50 μg mL ), 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 (), NADPH oxidase 4 (), Vanin-1 (), and steroidogenic acute regulatory protein () genes. Additionally, we examined antioxidant genes, including glutathione peroxidase (), catalase (), and superoxide dismutase ().
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 , , and by 0.27, 0.24, and 0.44, respectively. In the ALA treatment group, the fold expression of , , and exceeded that in the untreated group (1.2, 1.02, and 1.7, respectively). GLY decreased the expression of the and genes while increasing the expression of the and genes compared to the control group. Furthermore, ALA decreased and expression in GCs and increased and 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.
草甘膦(GLY)暴露与流产和早产的较高发生率之间存在关联。本研究旨在评估α-硫辛酸(ALA)对人GLY处理的颗粒细胞(GCs)卵泡发生基因表达和氧化应激的影响。
从46名患有输卵管或男性不育因素的健康女性中获取颗粒细胞。将颗粒细胞培养并用GLY(250μg/mL)、ALA(50μg/mL)或250 GLY + 50 ALA处理24小时。使用DAPI染色和流式细胞术评估ALA对细胞凋亡的影响。我们使用实时PCR评估处理后颗粒细胞中几个基因的表达。我们观察了叉头框蛋白O1(FOXO1)、NADPH氧化酶4(NOX4)、血管生成素-1(VNN1)和类固醇生成急性调节蛋白(STAR)基因。此外,我们检测了抗氧化基因,包括谷胱甘肽过氧化物酶(GPX)、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)。
与GLY处理组相比,ALA处理组和GLY + ALA组的DNA片段化不那么明显。ALA处理分别降低了GLY处理组和GLY + ALA组合中的凋亡率(5.5%和19.6% vs. 35.8%)。GLY分别使FOXO1、NOX4和VNN1的表达倍数降低了0.27倍、0.24倍和0.44倍。在ALA处理组中,FOXO1、NOX4和VNN1的表达倍数超过未处理组(分别为1.2倍、1.02倍和1.7倍)。与对照组相比,GLY降低了GPX和CAT基因的表达,同时增加了NOX4和VNN1基因的表达。此外,ALA降低了颗粒细胞中NOX4和VNN1的表达,并增加了GPX和CAT基因的表达。
暴露于GLY会诱导细胞凋亡,而ALA会增加颗粒细胞中抗氧化基因的表达。此外,可推荐使用ALA来减少氧化剂对女性生殖系统造成伤害。