Age-dependent changes in the expression of superoxide dismutases and catalase are associated with ultrastructural modifications in human granulosa cells

Abstract

Limited knowledge exists about changes in follicle quality associated with age. The aim of this work was to investigate whether ageing may cause oxidative stress-mediated alterations in human granulosa cells (GCs) from periovulatory follicles. GCs employed in this study were obtained from follicular aspirates of 20 younger women (range 27-32 years) and 20 older women (range 38-41 years) undergoing an IVF treatment. Results obtained from comparative RT-PCR analysis revealed that the mean relative levels of mRNAs coding for superoxide dismutases, Cu, ZnSOD (SOD1), MnSOD (SOD2) and catalase were significantly decreased in women ³38 years (P < 0.05, Student's t-test). These changes were associated with a reduced expression of SOD1, SOD2 and catalase at the protein level. When examined at an ultrastructural level, most of the GCs from this group showed defective mitochondria and fewer lipid droplets than those observed in the younger group. These results indicate that GCs from older patients suffer from age-dependent oxidative stress injury and are taken as an evidence for reduced defence against reactive oxygen species (ROS) in GCs during reproductive ageing.

Differences in cumulus cells gene expression between modified natural and stimulated in vitro fertilization cycles

“…The correlation between patients' age and log2 expression values for genes related to oxidation-reduction process, regardless of therapy, is not statistically significant. A negative correlation between age and gene expression of genes involved in defense against reactive oxygen species (ROS) in follicles is well known and has been reported in several studies [28][29][30][31]. It seems that in our study we have controlled this effect by including patients of similar age and younger than 35 years, which is proved by a non-significant correlation (Table S3-Regardless of therapy).…”

Age-associated changes in bovine oocytes and granulosa cell complexes collected from early antral follicles

“…In aging cells, high amount of reactive oxygen species (ROS) are usually generated due to age-associated decrease in mitochondrial quality. A decrease in the levels of SOD1, SOD2, and catalase mRNA and protein in granulosa cells derived from antral follicles of older women (≥38 years) has been reported [18]. In addition, p38 MAPK was more extensively phosphorylated in the granulosa cells derived from older women (>36) than those derived from younger patients, and the activation and cytoplasmic localization of p38 MAPK in granulosa cells derived from older women was indicative of oxidative stress [20].…”

“…Oocyte growth is supported by surrounding granulosa cells [17], and a deterioration in the characteristics of these granulosa cells derived from full-grown antral follicles have been observed in aged women and cows [18][19][20][21]. Result from real time RT-PCR experiments have revealed that the expression of some genes including those that encode for antioxidants in mouse ovary was affected by aging [22].…”

Age-related Accumulation of Non-heme Ferric and Ferrous Iron in Mouse Ovarian Stroma Visualized by Sensitive Non-heme Iron Histochemistry

“…Thus, there is a delicate balance between ROS and antioxidant enzymes in the ovarian tissue (Shiotani et al 1991;Behrman et al 2001;Sugino et al 2004;Agarwal et al 2005;Agarwal et al 2006;Tatone et al 2008). The imbalance of ROS and antioxidants has been suggested as a mechanism of ovarian aging, as shown by decreased levels of glutathione and glutathione S-transferase in ovulated oocytes from aged mouse or downregulation of superoxide dismutase (Cu/ZnSOD and MnSOD) and catalase genes in human granulosa cells (Tarin et al 2004;Tatone et al 2006;Tatone et al 2008). Under these conditions, increased redox-active iron in aged ovaries would be a pro-oxidant for the generation of toxic ROS such as hydroxyl radicals, resulting in a loss of the balance between ROS and antioxidants.…”