Regulation of the ovarian oxidative status by leptin during the ovulatory process in rats

Abstract

Leptin exerts both stimulatory and inhibitory effects on the ovulatory process. In this study, we investigated whether these opposite effects involve changes in the oxidative status in response to different levels of leptin. To this end, we performed both in vivo and in vitro assays using ovaries of immature rats primed with gonadotropins to induce ovulation. Superoxide dismutase (SOD) and catalase (CAT) activity, lipid peroxidation, glutathione (GSH) content, and reactive oxygen species (ROS) were studied as oxidative damage-related parameters. The expression of BCL2, BAX, and caspase 3 were measured by western blot as apoptosis-related biomarkers. The acute treatment with leptin, which inhibits ovulation, decreased SOD activity and increased active caspase 3 expression. No differences were found in CAT activity, lipid peroxidation, or total GSH. In contrast, the daily administration of leptin, which induces ovulation, decreased GSH content, ROS levels, and Bax and active caspase 3 expression, but caused no changes in other parameters. In addition, the daily administration of leptin induced follicular growth, measured by the number of antral follicles in ovarian sections. Using ovarian explant cultures, we found increased BCL2 expression and decreased SOD activity at low and high concentrations of leptin respectively. Thus, leptin can modulate the oxidative status of the ovarian tissue, during the ovulatory process, by acting on different targets according to its circulating levels. At low concentration, leptin seems to play a protective role against the oxidative stress, whereas at high concentrations, this protein seems to be involved in cell death.

Leptin induces ROS via NOX5 in healthy and neoplastic mammary epithelial cells

“…Whatever the cell line, leptin briefly increased ROS production, which remained significantly higher than basal level for more than 1 h. This study demonstrates for the first time that leptin is involved in short-term ROS production in epithelial mammary cells. The results are in agreement with previous work linking leptin to oxidative stress in other cell types such as endothelial cells, hepatic epithelial cells, cardiac myofibroblasts and ovarian cells (22,23,25,35). However, leptin did not present a difference of effect despite our hypothesis on hyperleptinemia due to obesity.…”

“…Leptin is upregulated in obesity where it is involved in critical steps of cell homeostasis from cell growth (19) to metabolism (20) and energy production (21). A crosslink between ROS production and leptin signalling has been reported in several tissues including endothelium (22) and ovaries (23), and could be one of the signaling pathways activated through the leptin receptor OB-R in the presence of leptin (24). However, there is surprisingly little data on how leptin affects oxidative stress, especially in cancer (25).…”

Nanosilver particles increase follicular atresia: Correlation with oxidative stress and aromatization

“…To understand how NSPs result in oxidative stress, one should note the role of SOD in neutralizing the ROS production as well as its importance in protecting the growing follicles against ROS. 44,45 Therefore, increased follicular atresia in ovaries of the NSPs-received animals could be attributed to diminished SOD level, which in turn resulted in progressive ROS-related damages. Ultimately, the NSPsinduced progressive oxidative stress promoted the lipid peroxidation (note Figure 5).…”

“…Indeed, the ROS is involved in modulation of ovarian physiological functions, including maturation of oocyte, ovarian steroidogenesis, corpus luteal function, and leukocytes infiltration Considering increased follicular atresia associated with decreased antioxidant status, we can come close to this fact that NSPs at different dose levels exert their detrimental impact partially by inducing oxidative stress. To understand how NSPs result in oxidative stress, one should note the role of SOD in neutralizing the ROS production as well as its importance in protecting the growing follicles against ROS . Therefore, increased follicular atresia in ovaries of the NSPs‐received animals could be attributed to diminished SOD level, which in turn resulted in progressive ROS‐related damages.…”

Perfluorooctanoic acid disrupts gap junction intercellular communication and induces reactive oxygen species formation and apoptosis in mouse ovaries

“…DCFDA diffuses into the cells, where it is converted by non‐specific esterases to the nonfluorescent compound dichlorofluorescein (H 2 DCF), which is, in turn, oxidized by hydrogen peroxide to the fluorescent DCF. Therefore, the average fluorescent intensity of DCF is a surrogate measure of intracellular ROS levels . After incubation with DCFDA, ovaries were washed with PBS, embedded in cryostat sectioning medium and frozen at −20°C.…”