Thyroid dysfunction and aneuploidy in offspring

The intercommunication between thyroid gland dysfunction in parents and aneuploid karyotype formation in offspring was studied using cytogenetic and immunogenetic approaches. It was determined, that increased risk for children being born with Down or Turner diseases depends upon a presence of following HLA-antigenes in parents, partcularly in motheritract. The intercommunication between thyroid gland dysfunction in parents and aneuploid karyotype formation in offspring was studied using cytogenetic and immunogenetic approaches. It was determined, that increased risk for children being born with Down or Turner diseases depends upon a presence of following HLA-antigenes in parents, particularly in mother's genome: B10, B40, B41, B51 and allele DQA*0301 of gene DQA of major histocompatibility complex. The presence of antigens B40, B51 and allele DQA*0301 was also associated with autoimmune thyroiditis. Thus, thyroid gland function disturbance, namely autoimmune thyroiditis can be considered as a risk factor of aneuploid karyotype formation.     

Hyperthermia-induced embryonic aneuploidy in mice

Chromosomal aneuploidy, as an effect of elevated ambient temperature during early gestation, was studied in 650 eight-day embryos from 60 females of two different mouse stocks. Exposure of treatment females to 34 C and 50% relative humidity during days 5 and 6 of gestation caused an increase in embryo chromosomal hyperploidy. No embryo sex interaction with the percent hyperploidy was found.     

Tetraploidy, aneuploidy and cancer

Aneuploidy is one of the most obvious differences between normal and cancer cells. However, there remains debate over how aneuploid cells arise and whether or not they are a cause or consequence of tumorigenesis. One proposed route to aneuploid cancer cells is through an unstable tetraploid intermediate. Supporting this idea, recent studies demonstrate that tetraploidy promotes chromosomal aberrations and tumorigenesis in vivo. These tetraploid cells can arise by a variety of mechanisms, including mitotic slippage, cytokinesis failure, and viral-induced cell fusion. Furthermore, new studies suggest that there might not be a ploidy-sensing checkpoint that permanently blocks the proliferation of tetraploid cells. Therefore, abnormal division of tetraploid cells might facilitate genetic changes that lead to aneuploid cancers.     

Causes and consequences of aneuploidy in cancer

Genetic instability, which includes both numerical and structural chromosomal abnormalities, is a hallmark of cancer. Whereas the structural chromosome rearrangements have received substantial attention, the role of whole-chromosome aneuploidy in cancer is much less well-understood. Here we review recent progress in understanding the roles of whole-chromosome aneuploidy in cancer, including the mechanistic causes of aneuploidy, the cellular responses to chromosome gains or losses and how cells might adapt to tolerate these usually detrimental alterations. We also explore the role of aneuploidy in cellular transformation and discuss the possibility of developing aneuploidy-specific therapies.     

Predisposition to aneuploidy in the oocyte

While the incidence of predisposition to aneuploidy in the oocyte increases with age, there is also evidence of increased incidence in young women with recurrent miscarriage, recurrent aneuploidy, or recurrent implantation failure after in vitro fertilization. There is evidence from mouse models and from observations in humans that follicle-stimulating hormone (FSH) probably has a direct or indirect effect on the occurrence of oocyte aneuploidy. It seems that increased endogenous or exogenous FSH could induce meiotic disruption. Although the effect of FSH may explain the age-related increase in aneuploidy rate, many questions remain regarding young women, even if their FSH level is sometimes increased. Disruption of meiotic gene expression caused by exposure to environmental contaminants or by gene defects could also predispose to oocyte aneuploidy. Such abnormalities could impact on the oocyte pool, recombination and synapsis during fetal life, or oocyte growth.     

Mosaic aneuploidy in early fetal losses

Chromosomal mosaicism is the presence of 2 or more cell lines with different karyotypes in the same individual. Mosaic karyotypes are a remarkable feature of early stages of human embryo development. They result from mitotic errors in chromosome segregation and demonstrate the clearest example of somatic mutagenesis in human beings. This review is devoted to the classification of chromosomal mosaicism and the analysis of its underlying mechanisms, incidence and phenotypic effects during embryo development. A model for tissue-specific aneuploid cell line compartmentalization in spontaneous abortions is introduced.     

Sister chromatid cohesion control and aneuploidy

Apart from a personal tragedy, could Down syndrome, cancer and infertility possibly have something in common? Are there links between a syndrome with physical and mental problems, a tumor growing out of control and the incapability to reproduce? These questions can be answered if we look at the biological functions of a protein complex, named cohesin, which is the main protagonist in the regulation of sister chromatid cohesion during chromosome segregation in cell division. The establishment, maintenance and removal of sister chromatid cohesion is one of the most fascinating and dangerous processes in the life of a cell. Errors in the control of sister chromatid cohesion frequently lead to cell death or aneuploidy. Recent results showed that cohesins also have important functions in non-dividing cells, revealing new, unexplored roles for these proteins in human syndromes, currently known as cohesinopathies. In the last 10 years, we have improved our understanding of the molecular mechanisms of the cohesin and cohesin-interacting proteins regulating the different events of sister chromatid cohesion during cell division in mitosis and meiosis.     

Stable variants of sperm aneuploidy among healthy men show associations between germinal and somatic aneuploidy

Repeated semen specimens from healthy men were analyzed by sperm fluorescence in situ hybridization (FISH), to identify men who consistently produced elevated frequencies of aneuploid sperm and to determine whether men who were identified as stable variants of sperm aneuploidy also exhibited higher frequencies of aneuploidy in their peripheral blood lymphocytes. Seven semen specimens were provided by each of 15 men over a 2-year period and were evaluated by the X-Y-8 multicolor sperm FISH method (i.e., approximately 1,050,000 sperm were analyzed from 105 specimens). Three men were identified as stable aneuploidy variants producing significantly higher frequencies of XY, disomy X, disomy Y, disomy 8, and/or diploid sperm over time. In addition, one man and three men were identified as sperm-morphology and sperm-motility variants, respectively. Strong correlations were found between the frequencies of sperm with autosomal and sex-chromosome aneuploidies and between the two types of meiosis II diploidy; but not between sperm aneuploidy and semen quality. A significant association was found between the frequencies of sex-chromosome aneuploidies in sperm and lymphocytes in a subset of 10 men (r2=0.67, P=.004), especially between XY sperm and sex-chromosome aneuploidy in lymphocytes (r2=0.70, P=.003). These findings suggest that certain apparently healthy men can produce significantly higher frequencies of both aneuploid sperm and lymphocytes. Serious long-term somatic and reproductive health consequences may include increased risks of aneuploidy-related somatic diseases and of having children with paternally transmitted aneuploidies, such as Klinefelter, Turner, triple-X, and XYY syndromes.     

How to survive aneuploidy

Aneuploidy, or an abnormal number of chromosomes, adversely affects cell growth, but it is also linked with cancer and tumorigenesis. Now, Torres et al. (2010) help to resolve this paradox by demonstrating that aneuploid yeast cells can evolve mutations in the proteasome protein degradation pathway that alleviate imbalances in protein production and increase the cell's proliferative capacities.     

Frequency and distribution of aneuploidy in human female gametes

Summary During the past 6 years, 14 cytogenetic studies on human oocytes recovered during in vitro fertilization procedures have been published; they report contradictory results. The present survey has pooled the more than 1500 oocyte chromosome complements examined to date, in order to determine generalized trends in chromosomal abnormalities of female gametes. The overall frequency of abnormalities in mature oocytes is 24.0% with a large majority of aneuploidies (22.8%) over structural aberrations (1.2%), which could be explained by the difficulty in the detection of structural abnormalities in oocyte chromosome sets. An analysis of the distribution of non-disjunction among all chromosomes was also performed. In the A, C, D, and especially in the G groups, there is a significant difference between the observed non-disjunction and the frequencies expected from an equal partitioning of non-disjunction among all chromosomes. These data are discussed with reference to the differences obtained from cytogenetic studies on human sperm and from investigations on spontaneous abortion.