(3)排卵過程におけるメラトニンの防御的役割 : メラトニンは卵胞内で卵と顆粒膜細胞を酸化ストレスから護る(<特集>第61回学術講演会シンポジウム2「中枢神経関連生理活性物質の生殖機能へのかかわり」)

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Reactive oxygen species (ROS) are produced within the follicle especially during the ovulatory process. ROS play a physiological role in the process of ovulation, e.g. follicle rapture. However, excessive amount of ROS causes oxidative stress and damages oocytes and luteinized granulosa cells. On the other hand, antioxidant defense systems including superoxide dismutase (SOD) or glutathione (GSH) are present in follicles. The balance between ROS and antioxidants within the follicle seems to be critical for oocytes and luteinized granulosa cells. Melatonin, which is a hormone secreted by pineal gland, is known as a powerful free radical scavenger and a broad-spectrum antioxidant. We already reported that human preovulatory follicular fluids contain higher concentrations of melatonin than of plasma. Present study was undertaken to examine whether melatonin acts as an anti-oxidant within follicles and protects oocytes and granulosa cells from oxidative stress. To investigate the direct role of oxidative stress and melatonin on oocyte maturation, oocytes recovered from immature ICR mice (3weeks old) were incubated in medium with hydrogen peroxide (H_2O_2) and melatonin. Oocytes with first polar body were significantly decreased in medium with H_2O_2. Reduced percentages of the oocytes with first polar body caused by H_2O_2 were increased by melatonin addition. H_2O_2 inhibits oocytes maturation but melatonin revealed protective activity against oxidative stress caused by H_2O_2. Infertility women who were treated with a standardized IVF-ET protocol (GnRH analog long protocol) took 3mg tablets of melatonin orally at 22:00 from the fifth day of the previous menstrual cycle until the day before ovum pick up. Intrafollicular melatonin concentrations were significantly increased during the melatonin treatment cycle. The intrafollicular concentration of 8-OHdG (8-hydroxy-2'-deoxyguanosine) and HEL (Hexanoyl-lysine adduct) were decreased after melatonin treatment compared to those in the prior cycle. The fertilization rate and pregnancy rate were improved by melatonin treatment. To investigate the relation between melatonin and luteal function, melatonin and progesterone concentrations in the matured follicles were measured by RIA, and 8-OHdG was determined by ELISA kit. Melatonin showed a positive correlation with progesterone and a negative correlation with 8-OHdG, and there was a negative correlation between progesterone and 8-OHdG. Luteinized granulosa cells collected from follicular fluids of IVF-ET patients were incubated with H_2O_2 and melatonin. Melatonin addition did not affect progesterone production by luteinized granulosa cells. Progesterone production was significantly inhibited by H_2O_2 in a dose-dependent manner. The inhibitory effect of H_2O_2 on progesterone production was significantly blocked by melatonin. Melatonin seems to play an important role as an anti-oxidant in the follicle. Melatonin protects oocytes and granulosa cells from ROS during the ovulatory process, and contributes to oocyte maturation and luteinization of granulosa cells.
2009-10-01

(3)排卵過程におけるメラトニンの防御的役割 : メラトニンは卵胞内で卵と顆粒膜細胞を酸化ストレスから護る(<特集>第61回学術講演会シンポジウム2「中枢神経関連生理活性物質の生殖機能へのかかわり」)

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