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Fertility is an age-related phenomenon which is characterized by the gradual loss with advancing age until the appearance of menopause. This event is naturally accompanied by a gradual decline in the quality and number of ovarian follicles (1,2). Aging is related to functional organ impairment due to the progressive storage of free radicals in the normal cell metabolism and is examined as one chief mechanism indicating ovarian aging (3) Free radicals are introduced as remarkable factors which affect oocyte quality. It is shown that aging in a woman is associated with lower antioxidant activity due to lipid peroxidation, enzyme inactivation, protein oxidation, and even DNA distribution (4-6). In fact, reactive oxygen species (ROS) can potentially disturb the balance of physiological processes in the ovary (7,8) by follicle apoptosis (6,9). Thus, it seems that oxidative stress has an important role in the decrease of fertility by increasing age. In this regard, the use of antioxidant agents may decrease age-related infertility processing (9). Curcumin is a natural polyphenol in the rhizome of Curcuma longa using as a flavor because of its antiinflammatory, anti-oxidant, and anti-apoptotic features (10). In addition, curcumin can target and inhibit multiple signaling molecules related to systemic inflammation, degenerative conditions, and stress oxidative (11,12). Based on a recent report, curcumin has beneficial effects and can play a crucial role in keeping ovarian oocytes from oxidative stress by increasing tissue anti-oxidant marker levels while decreasing apoptosis (13). Considering the above-mentioned explanation, the present study attempted to demonstrate whether curcumin can effectively prevent apoptosis in the ovary during the process of aging in mice until the age of 33week. To this end, a novel method was used to determine the relationship of the apoptosis with advancing maternal age by subjecting female mice to daily administration of curcumin after prepubertal influences on oocyte quality on the verge of reproductive failure during a 33-week investigation. Abstract Objectives: Oxidative stress can initiate the process of apoptosis which affects the oocyte quality and reduces development competency in the ovarian follicles. Accordingly, the present study determined the effects of curcumin as a well-known antioxidant on the apoptosis prevention of mature oocytes during the natural increasing age in female mice. Materials and Methods: In this case-control, interventional, and quantitative applied research, 21-day-old NMRI (Naval Medical Research Institute) female mice were used as control, vehicle, and curcumin groups. The mice in the curcumin group received 100 mg/kg/d curcumin intraperitoneally. After initial interventions, the Annexin-V-FLUOS staining was applied to evaluate the oocyte apoptosis rate in the three groups at 6, 12, and 33 weeks of age. The expression of oocytes apoptosis-related genes (Bcl2 and Bax) was also assessed by the real-time polymerase chain reaction (PCR) technique, followed by measuring oxidation-reduction markers in the ovaries. Results: Our results showed that oocyte apoptosis and necrosis in the curcumin group decreased in comparison with the control and vehicle groups at 12 and 33 weeks (P < 0.001). Moreover, the use of curcumin led to the upregulation of Bcl2 and downregulation of Bax genes at 6, 12, and 33 weeks (P < 0.001). In addition, the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities increased in the curcumin group compared with control and vehicle groups at 12 and 33 weeks (P < 0.001) while malondialdehyde (MDA) decreased in the curcumin group at 12 (P < 0.001), in the control at 12 (P < 0.01), and in the vehicle at 33 weeks (P < 0.01). Conclusions: In general, curcumin could suppress oocyte apoptosis through upregulating Bcl2 and the downregulating of Bax gene, as well as suppressing oxidative stress pathways involving oocyte apoptosis and necrosis.

Curcumin Delays Oocyte Apoptosis Through Overexpression of BCL-2 Gene in Young and Middle-Aged Mouse Models