DNA repair signalling pathway genes are overexpressed in poor-quality pre-implantation human embryos with complex aneuploidy.
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.


METHODS
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.
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.
Masood
M
Bazrgar
Department of Genetics at Reproductive Biomedicine Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. Electronic address: gourabi@royaninstitute.org.
Hamid
H
Gourabi
Department of Embryology at Reproductive Biomedicine Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Poopak Eftekhari
PE
Yazdi
Department of Genetics at Reproductive Biomedicine Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Hamed
H
Vazirinasab
Department of Genetics at Reproductive Biomedicine Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Mostafa
M
Fakhri
Department of Embryology at Reproductive Biomedicine Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Fatemeh
F
Hassani
Department of Embryology at Reproductive Biomedicine Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Mojtaba Rezazadeh
MR
Valojerdi
D000782:Aneuploidy; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D033041:Embryo Research; D004622:Embryo, Mammalian / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics
Aneuploidy; DNA damage; DNA repair; Embryo quality; Gene expression; Pre-implantation