Segregation In Embryos Research Articles

DO CLINIC SPECIFIC FACTORS IMPACT ANEUPLOIDY RATES IN TROPHECTODERM BIOPSY SAMPLES?

Previous literature has suggested that in vitro fertilization (IVF) processes and procedures could cause cellular stress that may impact mitotic chromosome segregation in embryos (Swain, 2019). In a study performed by Munne et al., 2017, the authors reported a strong association between clinic-specific IVF procedures and aneuploidy rates detected on preimplantation genetic testing for aneuploidy (PGT-A) using an array comparative genomic hybridization (aCGH) platform.

The paternal effect of chromosome translocation carriers observed from meiotic segregation in embryos

Human translocation carriers may present alterations in meiosis. Understanding the mechanism of meiotic segregation of reciprocal translocations is important for estimation of the risk of either pregnancy loss or birth defects. The objective of this work was to estimate meiotic segregation rates in preimplantation embryos from preimplantation genetic diagnosis (PGD) cycles of female and male reciprocal translocation carriers. In 20 cycles for 14 couples, PGD was performed on 118 day three embryos using fluorescence in situ hybridization (FISH) with specific probes for each translocation. The meiotic segregation modes and the effect of the paternal origin of translocated carrier were estimated. Overall, the proportions of alternate segregation for normal or balanced chromosome contents in preimplantation embryos from PGD cycles in reciprocal male and female carriers were not significantly different (35.5 versus 23.8%). However, the frequencies of adjacent-1 and adjacent-2 segregation were lower in embryos from female reciprocal translocation carriers than from male carriers. For male translocations, alternate segregation was the most frequent mode. The proportion of 3:1 segregation was the most frequent in female translocations carriers. We report differences in segregation modes in embryos obtained from PGD cycles according to the gender of reciprocal translocation carrier. However, these differences did not affect the proportion of balanced embryos and the take home baby rate. The analysis of the meiotic behaviour of chromosomes and the differences between the meiotic products of female and male for a chromosomal rearrangement could help predict the outcome of PGD for translocation carriers.

Mars and tousled-like kinase act in parallel to ensure chromosome fidelity in Drosophila

BackgroundHigh levels of Hepatoma Up-Regulated Protein (HURP) and Tousled-Like Kinase (TLK) transcripts are found in hepatocellular carcinoma. HURP overexpression induces anchorage-independent growth of 293-T cells and enhances a rough-eye phenotype resulting from tlk overexpression in Drosophila. In addition, both HURP and Mars, a Drosophila HURP sequence homologue, promote polymerization of mitotic spindles. Thus, the genetic interaction of mars with tlk might be required for accurate chromosome segregation.MethodsTo reveal whether chromosome fidelity was decreased, the frequency of gynandromorphy, an individual with both male and female characteristics, and of non-disjunction were measured in the progeny from parents with reduced mars and/or tlk activities and analyzed by Student's t-test. To show that the genetic interaction between mars and tlk is epistatic or parallel, a cytological analysis of embryos with either reduced or increased activities of mars and/or tlk was used to reveal defects in mitotic-spindle morphology and chromosome segregation.ResultsA significant but small fraction of the progeny from parents with reduced mars activity showed gynandromorphy and non-disjunction. Results of cytological analysis revealed that the decrease in chromosome fidelity was a result of delayed polymerization of the mitotic spindle, which led to asynchronous chromosome segregation in embryos that had reduced mars activity. By removing one copy of tousled-like kinase (tlk) from flies with reduced mars activity, chromosome fidelity was further reduced. This was indicated by an increased in the non-disjunction rate and more severe asynchrony. However, the morphology of the mitotic spindles in the embryos at metaphase where both gene activities were reduced was similar to that in mars embryos. Furthermore, tlk overexpression did not affect the morphology of the mitotic spindles and the cellular localization of Mars protein.ConclusionChromosome fidelity in progeny from parents with reduced mars and/or tlk activity was impaired. The results from cytological studies revealed that mars and tlk function in parallel and that a balance between mars activity and tlk activity is required for cells to progress through mitosis correctly, thus ensuring chromosome fidelity.

Transcriptional regulation of Notch and Delta: requirement for neuroblast segregation in Drosophila.

Segregation of a single neural precursor from each proneural cluster in Drosophila relies on Notch-mediated lateral signalling. Studies concerning the spacing of precursors for the microchaetes of the peripheral nervous system suggested the existence of a regulatory loop between Notch and its ligand Delta within each cell that is under transcriptional control. Activation of Notch leads to repression of the achaete-scute genes which themselves regulate transcription of Delta, perhaps directly. Here we have tested a requirement for transcriptional regulation of Notch and/or Delta during neuroblast segregation in embryos, by providing Notch and Delta ubiquitously at uniform levels. Neuroblast segregation occurs normally under conditions of uniform Notch expression. Under conditions of uniform Delta expression, a single neuroblast segregates from each proneural group in 80% of the cases, more than one in the remaining 20%. Thus transcriptional regulation of Delta is largely dispensable. We discuss the possibility that segregation of single precursors in the central nervous system may rely on a heterogeneous distribution of neural potential between different cells of the proneural group. Notch signalling would enable all cells to mutually repress each other and only a cell with an elevated neural potential could overcome this repression.