Endometrial receptivity: miRNAs signing in?

Editoria

Errors in chromosome segregation during oogenesis and early embryogenesis

Errors in chromosome segregation occurring during human oogenesis and early embryogenesis are very common. Meiotic chromosome development during oogenesis is subdivided into three distinct phases. The crucial events, including meiotic chromosome pairing and recombination, take place from around 11 weeks until birth. Oogenesis is then arrested until ovulation, when the first meiotic division takes place, with the second meiotic division not completed until after fertilization. It is generally accepted that most aneuploid fetal conditions, such as trisomy 21 Down syndrome, are due to maternal chromosome segregation errors. The underlying reasons are not yet fully understood. It is also clear that superimposed on the maternal meiotic chromosome segregation errors, there are a large number of mitotic errors taking place post-zygotically during the first few cell divisions in the embryo. In this chapter, we summarise current knowledge of errors in chromosome segregation during oogenesis and early embryogenesis, with special reference to the clinical implications for successful assisted reproduction

Network coding as a coloring problem (Invited paper)

We consider a multicast configuration with two sources, and translate the network code design problem to vertex coloring of an appropriately defined graph. This observation enables to derive code design algorithms and alphabet size bounds, as well as establish a connection with a number of well-known results from discrete mathematics that increase our insight in the different trade-offs possible for network coding

Broadcast erasure channel with feedback: The two multicast case - Algorithms and bounds

We consider the single hop broadcast packet erasure channel (BPEC) with two multicast sessions (each of them destined to a different group of N users) and regularly available instantaneous receiver ACK/NACK feedback. Using the insight gained from recent work on BPEC with unicast and degraded messages [1], [2], we propose a virtual queue based session-mixing algorithm, which does not require knowledge of channel statistics and achieves capacity for N = 2 and iid erasures. Since the extension of this algorithm to N > 2 is not straightforward, we describe a simple algorithm which outperforms standard timesharing for arbitrary N and is actually asymptotically better than timesharing, for any finite N, as the erasure probability goes to zero. We finally provide, through an information-theoretic analysis, sufficient but not necessary asymptotic conditions between N and n (the number of transmissions) for which the achieved sum rate, under any coding scheme, is essentially identical to that of timesharing. © 2013 IEEE

Polymorphisms in the MTHFR gene influence embryo viability and the incidence of aneuploidy

MTHFR is an important enzyme in the metabolism of folic acid and is crucial for reproductive function. Variation in the sequence of MTHFR has been implicated in subfertility, but definitive data are lacking. In the present study, a detailed analysis of two common MTHFR polymorphisms (c.677C>T and c.1298A>C) was performed. Additionally, for the first time, the frequencies of different MTHFR alleles were assessed in preimplantation embryos. Several striking discoveries were made. Firstly, results demonstrated that maternal MTHFR c.1298A>C genotype strongly influences the likelihood of a pregnancy occurring, with the 1298C allele being significantly overrepresented amongst women who have undergone several unsuccessful assisted reproductive treatments. Secondly, parental MTHFR genotypes were shown to affect the production of aneuploid embryos, indicating that MTHFR is one of the few known human genes with the capacity to modulate rates of chromosome abnormality. Thirdly, an unusual deviation from Hardy-Weinberg equilibrium was noted for the c.677C>T polymorphism in subfertile patients, especially those who had experienced recurrent failure of embryo implantation or miscarriage, potentially explained by a rare case of heterozygote disadvantage. Finally, a dramatic impact of the MTHFR 677T allele on the capacity of chromosomally normal embryos to implant is described. Not only do these findings raise a series of interesting biological questions, but they also argue that testing of MTHFR could be of great clinical value, identifying patients at high risk of implantation failure and revealing the most viable embryos during in vitro fertilisation (IVF) cycles

SNP microarray-based 24 chromosome aneuploidy screening is significantly more consistent than FISH

Many studies estimate that chromosomal mosaicism within the cleavage-stage human embryo is high. However, comparison of two unique methods of aneuploidy screening of blastomeres within the same embryo has not been conducted and may indicate whether mosaicism has been overestimated due to technical inconsistency rather than the biological phenomena. The present study investigates the prevalence of chromosomal abnormality and mosaicism found with two different single cell aneuploidy screening techniques. Thirteen arrested cleavage-stage embryos were studied. Each was biopsied into individual cells (n = 160). The cells from each embryo were randomized into two groups. Those destined for FISH-based aneuploidy screening (n = 75) were fixed, one cell per slide. Cells for SNP microarray-based aneuploidy screening (n = 85) were put into individual tubes. Microarray was significantly more reliable (96%) than FISH (83%) for providing an interpretable result (P = 0.004). Markedly different results were obtained when comparing microarray and FISH results from individual embryos. Mosaicism was significantly less commonly observed by microarray (31%) than by FISH (100%) (P = 0.0005). Although FISH evaluated fewer chromosomes per cell and fewer cells per embryo, FISH still displayed significantly more unique genetic diagnoses per embryo (3.2 ± 0.2) than microarray (1.3 ± 0.2) (P < 0.0001). This is the first prospective, randomized, blinded and paired comparison between microarray and FISH-based aneuploidy screening. SNP microarray-based 24 chromosome aneuploidy screening provides more complete and consistent results than FISH. These results also suggest that FISH technology may overestimate the contribution of mitotic error to the origin of aneuploidy at the cleavage stage of human embryogenesis

Methods for comprehensive chromosome screening of oocytes and embryos: capabilities, limitations, and evidence of validity

Preimplantation aneuploidy screening of cleavage stage embryos using fluorescence in situ hybridization (FISH) may no longer be considered the standard of care in reproductive medicine. Over the last few years, there has been considerable development of novel technologies for comprehensive chromosome screening (CCS) of the human genome. Among the notable methodologies that have been incorporated are whole genome amplification, metaphase and array based comparative genomic hybridization, single nucleotide polymorphism microarrays, and quantitative real-time PCR. As these methods become more integral to treating patients with infertility, it is critical that clinicians and scientists obtain a better understanding of their capabilities and limitations. This article will focus on reviewing these technologies and the evidence of their validity

Aneuploidy in pluripotent stem cells and implications for cancerous transformation

Owing to a unique set of attributes, human pluripotent stem cells (hPSCs) have emerged as a promising cell source for regenerative medicine, disease modeling and drug discovery. Assurance of genetic stability over long term maintenance of hPSCs is pivotal in this endeavor, but hPSCs can adapt to life in culture by acquiring non-random genetic changes that render them more robust and easier to grow. In separate studies between 12.5% and 34% of hPSC lines were found to acquire chromosome abnormalities over time, with the incidence increasing with passage number. The predominant genetic changes found in hPSC lines involve changes in chromosome number and structure (particularly of chromosomes 1, 12, 17 and 20), reminiscent of the changes observed in cancer cells. In this review, we summarize current knowledge on the causes and consequences of aneuploidy in hPSCs and highlight the potential links with genetic changes observed in human cancers and early embryos. We point to the need for comprehensive characterization of mechanisms underpinning both the acquisition of chromosomal abnormalities and selection pressures, which allow mutations to persist in hPSC cultures. Elucidation of these mechanisms will help to design culture conditions that minimize the appearance of aneuploid hPSCs. Moreover, aneuploidy in hPSCs may provide a unique platform to analyse the driving forces behind the genome evolution that may eventually lead to cancerous transformation