O-35: Over-Expression of XRCC1 As Potential Biomarker for Poor Prognosis in Human Preimplantation Embryos: Selection by Study of 84 Genes Involved in DNA Damage Signaling Pathways

Background: Chromosome abnormalities are associated with poor morphology and development in human preimplantation embryos, all together lead to poor outcomes. This study aimed to explore altered expression of DNA damage pathways in “poor morphological and development embryos with sever aneuploidies”. Materials and Methods: Surplus day-4 embryos of PGD cases were pooled in two groups: Poor prognos tic group included grade C to D embryos with abnormal rate of cell division and sever aneuploidies, more than one aneuploid chromosome in FISH based PGD of day-3, this group named as group 1; good prognostic group as control included grade A to B embryos with normal rate of cell division without aneuploidy or mild aneuploid, just for one chromosome in day-3 PGD. Total RNA was isolated and reverse transcribed from each biological replicate included 15-20 embryos. Synthesis of cDNA was done by using of about 2 ng of RNA from each biological replicate. Gene expression of DNA damage signaling pathways was analyzed using commercial real-time PCR-based array including 84 genes of interest after specific preamplification of cDNA by a primer mix included all genes of array plate. Results: RPL13A was used as housekeeping gene for normalization of data based on the results of experiments. XRCC1 were over-expressed (p=0.001) in group 1. CDK7, DDIT3, FEN1, LIG1, MSH3, RAD50 and ACTB also showed over-expression in group 1(p<0.05). Some other genes had considerable fold changes while their statistical significance need to more biological replicates. Conclusion: XRCC1, as a participant in the base excision repair of DNA single strand breaks, could be considered as a biomarker for preimplantation embryos with poor prognosis.