Masood Bazrgar1, Hamid Gourabi2, Poopak Eftekhari Yazdi3, Hamed Vazirinasab4, Mostafa Fakhri4, Fatemeh Hassani3, Mojtaba Rezazadeh Valojerdi3. 1. Department of Genetics at Reproductive Biomedicine Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, Tehran, Iran. 2. Department of Genetics at Reproductive Biomedicine Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. Electronic address: gourabi@royaninstitute.org. 3. Department of Embryology at Reproductive Biomedicine Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. 4. Department of Genetics at Reproductive Biomedicine Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Abstract
OBJECTIVE: Chromosomal abnormalities and poor quality are correlated with DNA damage in the pre-implantation stage in humans. This study aimed to explore the altered expression of DNA damage signalling pathways - including apoptosis, cell cycle and DNA repair pathways - in poor-quality pre-implantation human embryos with complex aneuploidy. STUDY DESIGN: Surplus Day 4 embryos from candidates undergoing pre-implantation genetic screening were pooled into two groups. Group 1 included good-quality embryos that had simple aneuploidy, a single chromosome [according to fluorescence in situ hybridization-based pre-implantation genetic diagnosis (PGD) on Day 3], a normal rate of cell division, and graded as A or B (excellent to good). Group 2 included embryos with more than one aneuploid chromosome on PGD on Day 3, an abnormal rate of cell division, and graded as C or D (fair to poor). Gene expression of DNA damage signalling pathways was analysed using a real-time polymerase chain reaction-based array, which included 84 genes after specific pre-amplification of cDNA by a primer mix, including all array genes. RESULTS: In Group 2, five of the 84 genes studied showed significant overexpression (p<0.05): MSH3, XRCC1, RAD50, LIG1 and CDK7. Alterations were in agreement with genetic relationships in pathway analyses on DAVID. CONCLUSIONS: The five overexpressed genes are involved in DNA repair. Therefore, in comparison with cell cycle control and apoptotic pathways, DNA repair pathways are more activated in poor-quality pre-implantation human embryos with complex aneuploidy. This suggests that the dominant response to DNA damage in such embryos is DNA repair rather than cell division or apoptosis.
OBJECTIVE:Chromosomal abnormalities and poor quality are correlated with DNA damage in the pre-implantation stage in humans. This study aimed to explore the altered expression of DNA damage signalling pathways - including apoptosis, cell cycle and DNA repair pathways - in poor-quality pre-implantation human embryos with complex aneuploidy. STUDY DESIGN: Surplus Day 4 embryos from candidates undergoing pre-implantation genetic screening were pooled into two groups. Group 1 included good-quality embryos that had simple aneuploidy, a single chromosome [according to fluorescence in situ hybridization-based pre-implantation genetic diagnosis (PGD) on Day 3], a normal rate of cell division, and graded as A or B (excellent to good). Group 2 included embryos with more than one aneuploid chromosome on PGD on Day 3, an abnormal rate of cell division, and graded as C or D (fair to poor). Gene expression of DNA damage signalling pathways was analysed using a real-time polymerase chain reaction-based array, which included 84 genes after specific pre-amplification of cDNA by a primer mix, including all array genes. RESULTS: In Group 2, five of the 84 genes studied showed significant overexpression (p<0.05): MSH3, XRCC1, RAD50, LIG1 and CDK7. Alterations were in agreement with genetic relationships in pathway analyses on DAVID. CONCLUSIONS: The five overexpressed genes are involved in DNA repair. Therefore, in comparison with cell cycle control and apoptotic pathways, DNA repair pathways are more activated in poor-quality pre-implantation human embryos with complex aneuploidy. This suggests that the dominant response to DNA damage in such embryos is DNA repair rather than cell division or apoptosis.
Authors: Maria Vera-Rodriguez; Shawn L Chavez; Carmen Rubio; Renee A Reijo Pera; Carlos Simon Journal: Nat Commun Date: 2015-07-07 Impact factor: 14.919
Authors: Venu Perla; Marjan Nadimi; Rishi Reddy; Gerald R Hankins; Padma Nimmakayala; Robert T Harris; Jagan Valluri; Cristian Sirbu; Umesh K Reddy Journal: PLoS One Date: 2018-10-31 Impact factor: 3.240