O-158 The effect of circadian rhythm disruption due to constant light on ovarian and oocyte aging through possible relationship between PER2 and mTOR signaling pathway

Abstract

Study question Does circadian rhythm disruption by constant light affect the ovarian morphology and function, and cause ovarian and oocyte aging through possible relationship between PER2 and mTOR? Summary answer We demonstrated that circadian rhythm disruption by light may cause ovarian and oocyte aging. What is known already Circadian rhythm regulates multiple physiological processes and PER2 is one of the core circadian rhythm components. Changes in light conditions may cause circadian rhythm disruptions. Light exposure at night may cause attenuation in PER2 mRNA and protein levels. Circadian rhythm disruptions are thought to be associated with reproductive diseases. mTOR signaling pathway functions in folliculogenesis and oocyte maturation in ovary. Also, it is associated with ovarian and oocyte aging. Study design, size, duration A total of 32 female Balb/c mice which enter estrous cycle were used in the study. Mice were randomly assigned to one of two groups as 12:12h L:D and 12:12h L:L. During the experiment, 12:12h L:D (control group) was housed in a 12:12h light:dark cycle and 12:12h L:L (experiment group) was housed in a constant light conditions 12:12h light:light for 1 week. Participants/materials, setting, methods We housed 12:12h L:D group in standard lightening conditions and 12:12h L:L group in constant light for one week. We performed food intake and body weight change analysis. We evaluated ovarian morphology, follicle counting analysis. We evaluated ZP3 and nitrotyrosine (NTY) expression for oocyte aging markers. We performed western blot for PER2, mTOR, p-mTOR, p70 S6K, p-p70 S6K, and Caspase-3 protein levels. Main results and the role of chance We demonstrated that circadian rhythm disruption caused alteration in their food intake and decrease in primordial follicle numbers and increase in atretic follicles (p < 0.05). It caused increase in oxidative stress and decrease in ZP3 expression in oocytes (p < 0.05). We showed decreased protein levels of PER2, mTOR, p-mTOR and p70 S6K (p < 0.05). Limitations, reasons for caution The explanation of molecular mechanism underlying the relationship between circadian rhythm disruptions by light and ovarian function may lead the usage of circadian rhythm-based or light-based therapies currently using to treat some diseases on female reproductive system related diseases. Wider implications of the findings We conclude that constant light may reduce follicle reserve, cause follicles to go rapidly atresia and disrupt the oocyte quality, thus it may be a risk factor for female reproductive diseases such as premature ovarian insufficiency and early menopause. Trial registration number not applicable