Evaluation of the expression of molecular clock genes during placental development of normal and circadian rhythm disrupted mouse pregnancy

Objective: Circadian rhythm is the daily biological rhythm and regulated by 7 genes: Bmal1, Clock, Per1, Per2, Per3, Cry1 and Cry2.The placenta provides the communication between the mother and the fetus and rhythmically expresses the mature placental circadian clock genes. When these genes are disturbed during pregnancy, intrauterine growth retardation (IUGR) occurs. There is no information in literature about when the expression of the circadian clock genes starts in the placenta and whether the expression of these genes changes, when the rhythm is disrupted, in the placenta during pregnancy. The purpose of this study is to evaluate the IUGR formation, histomorphology of placental compartments and the rhythmic expression of circadian clock genes in pregnant mice groups, where their light cycle is normal and disturbed experimentally. Method: During pregnancy normal and disturbed light cycle groups were planned. Evidence of disturbance of the circadian rhythm was showed by locomotor activity tests. Zeitgeber (ZT) means time provider or synchronizer and defines a 24 hour period. Between ZT0-ZT12 is light and ZT12-ZT24 is dark. H-E staining was performed and mRNA expressions were determined by qRT-PCR at 12th, 14th and 16th days of pregnancy in the placentae of both groups. Results: When placenta of control group and group created by disrupting the circadian rhythm were compared, placentae of group created by disruption circadian rhythm was small, they showed histo-morphological defects and IUGR was present on fetuses, in all pregnancy days. It is found that the mouse placenta initiate the rhythmicity of circadian gene expressions from 12th day of embriyonic development, and changing the light/dark patterns disrupts the rhythmicity starting from the 12th day of pregnancy. Conclusion: We think that during placental development, the placental defects and the fetal IUGR occurrence might be caused by the disruption of the rhythmic expressions of the circadian genes. Key words: mouse placenta, circadian rhythm disruption, circadian clock genes, intrauterine growth retardation