Martín-Ramírez Rita, González-Fernández Rebeca, Rotoli Deborah, Hernández Jairo, Martín-Vasallo Pablo, Palumbo Angela, Ávila Julio
Laboratorio de Biología del Desarrollo, UD de Bioquímica y Biología Molecular and Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, La Laguna, Av. Astrofísico Sánchez s/n, 38206 La Laguna, Tenerife, Spain.
Institute of Endocrinology and Experimental Oncology (IEOS), CNR-National Research Council, 5-80131 Naples, Italy.
Int J Mol Sci. 2021 Mar 30;22(7):3596. doi: 10.3390/ijms22073596.
Regulation of oxidative stress (OS) is important to prevent damage to female reproductive physiology. While normal OS levels may have a regulatory role, high OS levels may negatively affect vital processes such as folliculogenesis or embryogenesis. The aim of this work was to study OS induced by glucose, a reactive oxygen species generator, or peroxynitrite, a reactive nitrogen species generator, in cultured human granulosa-lutein (hGL) cells from oocyte donors, analyzing expression of genes involved in oocyte maturation (FSHR, PAPP, and CYP19A1) and OS damage response (ALDH3A2). We also evaluated the effect of celastrol as an antioxidant. Our results showed that although both glucose and peroxynitrite produce OS increments in hGL cells, only peroxynitrite treatment increases ALDH3A2 and PAPP gene expression levels and decreases FSHR gene expression levels. Celastrol pre-treatment prevents this effect of peroxynitrite. Interestingly, when celastrol alone was added, we observed a reduction of the expression of all genes studied, which was independent of both OS inductors. In conclusion, regulation of OS imbalance by antioxidant substances such as celastrol may prevent negative effects of OS in female fertility. In addition to the antioxidant activity, celastrol may well have an independent role on regulation of gene expression in hGL cells.
氧化应激（OS）的调节对于防止女性生殖生理损伤至关重要。虽然正常的OS水平可能具有调节作用，但高水平的OS可能会对卵泡发生或胚胎发生等重要过程产生负面影响。这项工作的目的是研究由活性氧生成剂葡萄糖或活性氮生成剂过氧亚硝酸盐在来自卵母细胞供体的培养人颗粒黄体（hGL）细胞中诱导的OS，分析参与卵母细胞成熟（FSHR、PAPP和CYP19A1）和OS损伤反应（ALDH3A2）的基因表达。我们还评估了雷公藤红素作为抗氧化剂的作用。我们的结果表明，虽然葡萄糖和过氧亚硝酸盐都能使hGL细胞中的OS增加，但只有过氧亚硝酸盐处理会增加ALDH3A2和PAPP基因表达水平，并降低FSHR基因表达水平。雷公藤红素预处理可防止过氧亚硝酸盐的这种作用。有趣的是，当单独添加雷公藤红素时，我们观察到所有研究基因的表达均降低，这与两种OS诱导剂无关。总之，通过雷公藤红素等抗氧化物质调节OS失衡可能会防止OS对女性生育能力的负面影响。除了抗氧化活性外，雷公藤红素很可能在hGL细胞基因表达调节中具有独立作用。
