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Title: Molecular and cytogenetic investigation of chromosomal errors in human preimplantation development : possible causes
Author: Xanthopoulou, L.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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Chromosome abnormality is the leading cause of pregnancy loss, mental retardation and IVF failure in humans; it is a significant contributor to infertility and other disorders. Despite ~20 years of molecular cytogenetics in human embryos, many questions remain with respect to the origin, role, frequency and different causes of chromosomal errors at this stage. This thesis focuses on structural chromosomal abnormalities, chromosome breakage, binucleate cells, microsatellite instability and SYCP3 mutations. Carriers of structural abnormalities are at high risk of unfavourable meiotic segregation and production of unbalanced gametes/embryos. 396 biopsied blastomeres and 221 untransferred embryos from preimplantation genetic diagnosis (PGD) cycles were analysed by fluorescence in situ hybridisation (FISH). The aims were 1) to study the meiotic and mitotic behaviour in 19 reciprocal translocation carriers, and 2) in 2 intrachromosomal insertion carriers; 3) to investigate the overall level of chromosome breakage, meiotic aneuploidy, mosaicism and chromosome breakage, and 4) to assess whether advanced maternal age adversely affected PGD outcome in 59 PGD reciprocal translocations cycles. The frequency and chromosomal complement of biopsied binucleate cells (a common PGD complication) from 66 PGD and 151 PGS cycles were analysed to investigate the nature and origin of binucleate cells (aim 5). Proposed mechanisms of binucleation indicated that such cells should mostly be tetraploid; in this study however the majority appeared diploid. Microsatellite instability (MSI) has been previously associated with spontaneous abortions, thus DNA from 53 PGS embryos and their parents were analysed using ten polymorphic markers revealing an MSI frequency of 22%. SYCP3 occurs in the synaptonemal complex and is involved in chromosome synapsis. Previous reports associated SYCP3 mutations with recurrent pregnancy loss and azoospermia. DNA from 102 individuals undergoing PGS and 18 females with recurrent miscarriages were tested to investigate whether SYCP3 mutations are associated with infertility (aim 7). No mutations were identified.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available