Telomere Biology and Human Phenotype Turner, Kara J; Vasu, Vimal; Griffin, Darren K
Cells (Basel, Switzerland),
01/2019, Letnik:
8, Številka:
1
Journal Article
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Telomeres are nucleoprotein structures that cap the end of each chromosome arm and function to maintain genome stability. The length of telomeres is known to shorten with each cell division and it is ...well-established that telomere attrition is related to replicative capacity in vitro. Moreover, telomere loss is also correlated with the process of aging in vivo. In this review, we discuss the mechanisms that lead to telomere shortening and summarise telomere homeostasis in humans throughout a lifetime. In addition, we discuss the available evidence that shows that telomere shortening is related to human aging and the onset of age-related disease.
Preimplantation genetic testing for aneuploidies (PGT-A), with its vocal advocates and opponents, is at the epicentre of a perpetual, often heated, debate. The main issues include the following. ...First, how do we interpret the existing evidence-base? Around 100 retrospective and single-centre studies, two non-selection trials and at least two meta-analyses point to its efficacy in improving live birth rates, although randomized controlled trials are more mixed. Second, what should be done in relation to euploid/aneuploid mosaicism? Recent data suggest that low-level mosaic pregnancies can proceed uneventfully to term, so intelligent interpretation of the diagnostic data is appropriate. Third, what is the stance of the Human Fertilisation and Embryology Authority? The ‘traffic light’ system is much debated and is perhaps best described as well-intentioned, but misguided in places. Fourth, what is the motivation of people who maintain their point of view despite the evidence? Sadly, the presentation of new empirical evidence polarizes, rather than reconciles, opinion. Too many have made a career out of either promoting or denigrating PGT-A for them to back down easily. Finally, how can we find common ground and move forward? All patients should be counselled in a non-directive manner on whether to embark on PGT-A, summarizing for them the whole evidence base so they can make up their own mind.
To accurately determine mitochondrial DNA (mtDNA) levels in human blastocysts.
Retrospective analysis.
IVF clinic.
A total of 1,396 embryos derived from 259 patients.
Blastocyst-derived trophectoderm ...biopsies were tested by next-generation sequencing (NGS) and quantitative real-time polymerase chain reaction (qPCR).
For each sample the mtDNA value was divided by the nuclear DNA value, and the result was further subjected to mathematical analysis tailored to the genetic makeup of the source embryo.
On average the mathematical correction factor changed the conventionally determined mtDNA score of a given blastocyst via NGS by 1.43% ± 1.59% (n = 1,396), with maximal adjustments of 17.42%, and via qPCR by 1.33% ± 8.08% (n = 150), with maximal adjustments of 50.00%. Levels of mtDNA in euploid and aneuploid embryos showed a statistically insignificant difference by NGS (euploids n = 775, aneuploids n = 621) and by qPCR (euploids n = 100, aneuploids n = 50). Blastocysts derived from younger or older patients had comparable mtDNA levels by NGS ("young" age group n = 874, "advanced" age group n = 514) and by qPCR ("young" age group n = 92, "advanced" age group n = 58). Viable blastocysts did not contain significantly different mtDNA levels compared with unviable blastocysts when analyzed by NGS (implanted n = 101, nonimplanted n = 140) and by qPCR (implanted n = 49, nonimplanted n = 51).
We recommend implementation of the correction factor calculation to laboratories evaluating mtDNA levels in embryos by NGS or qPCR. When applied to our in-house data, the calculation reveals that overall levels of mtDNA are largely equal between blastocysts stratified by ploidy, age, or implantation potential.
Chromosomal mosaicism, the presence of two or more distinct cell lines, is prevalent throughout human pre- and post-implantation development and can lead to genetic abnormalities, miscarriages, ...stillbirths or live births. Due to the prevalence and significance of mosaicism in the human species, it is important to understand the origins, mechanisms and incidence of mosaicism throughout development.
Literature searches were conducted utilizing Pubmed, with emphasis on human pre- and post-implantation mosaicism.
Mosaicism persists in two separate forms: general and confined. General mosaicism is routine during human embryonic growth as detected by preimplantation genetic screening at either the cleavage or blastocyst stage, leading to mosaicism within both the placenta and fetus proper. Confined mosaicism has been reported in the brain, gonads and placenta, amongst other places. Mosaicism is derived from a variety of mechanisms including chromosome non-disjunction, anaphase lagging or endoreplication. Anaphase lagging has been implicated as the main process by which mosaicism arises in the preimplantation embryo. Furthermore, mosaicism can be caused by any one of numerous factors from paternal, maternal or exogenous factors such as culture media or possibly controlled ovarian hyperstimulation during in vitro fertilization (IVF). Mosaicism has been reported in as high as 70 and 90% of cleavage- and blastocyst-stage embryos derived from IVF, respectively.
The clinical consequences of mosaicism depend on which chromosome is involved, and when and where an error occurs. Mitotic rescue of a meiotic error or a very early mitotic error will typically lead to general mosaicism while a mitotic error at a specific cell lineage point typically leads to confined mosaicism. The clinical consequences of mosaicism are dependent on numerous aspects, with the consequences being unique for each event.
To assess the relationship between maternal age, chromosome abnormality, implantation, and pregnancy loss.
Multicenter retrospective study.
IVF centers in the United States.
IVF patients undergoing ...chromosome screening.
Embryo biopsy on day 3 or day 5/6 with preimplantation genetic diagnosis (PGD) by array comparative genomic hybridization.
Aneuploidy, implantation, pregnancy, and loss rates.
Aneuploidy rates increased with maternal age from 53% to 93% for day 3 biopsies and from 32% to 85% for blastocyst biopsies. Implantation rates for euploid embryos for ages <35-42 years did not decrease after PGD: ranges 44%-32% for day 3 and 51%-40% for blastocyst. Ongoing pregnancy rates per transfer did not decrease for maternal ages <42 years after PGD with day 3 biopsy (48.5%-38.1%) or blastocyst biopsy (64.4%-54.5%). Patients >42 years old had implantation rates of 23.3% (day 3), 27.7% (day 5/6), and the pregnancy rate with day 3 biopsy was 9.3% and with day 5 biopsy 10.3%.
Selective transfer of euploid embryos showed that implantation and pregnancy rates were not significantly different between reproductively younger and older patients up to age 42 years. Some patients who start an IVF cycle planning to have chromosome screening do not have euploid embryos available for transfer, a situation that increases with advancing maternal age. Mounting data suggests that the dramatic decline in IVF treatment success rates with female age is primarily caused by aneuploidy.
Egg and math: introducing a universal formula for egg shape Narushin, Valeriy G.; Romanov, Michael N.; Griffin, Darren K.
Annals of the New York Academy of Sciences,
December 2021, 2021-12-00, 20211201, Letnik:
1505, Številka:
1
Journal Article
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The egg, as
one of the most traditional food products, has long attracted the attention of mathematicians, engineers, and biologists from an analytical point of view. As a main parameter in ...oomorphology, the shape of a bird's egg has, to date, escaped a universally applicable mathematical formulation. Analysis of all egg shapes can be done using four geometric figures: sphere, ellipsoid, ovoid, and pyriform (conical or pear‐shaped). The first three have a clear mathematical definition, each derived from the expression of the previous, but a formula for the pyriform profile has yet to be derived. To rectify this, we introduce an additional function into the ovoid formula. The subsequent mathematical model fits a completely novel geometric shape that can be characterized as the last stage in the evolution of the sphere—ellipsoid—Hügelschäffer's ovoid transformation, and it is applicable to any egg geometry. The required measurements are the egg length, maximum breadth, and diameter at the terminus from the pointed end. This mathematical analysis and description represents the sought‐for universal formula and is a significant step in understanding not only the egg shape itself, but also how and why it evolved, thus making widespread biological and technological applications theoretically possible.
The shape of a bird's egg has escaped a universally applicable mathematical formulation. All egg shapes can be described as one of four geometric figures: sphere, ellipsoid, ovoid, and pyriform (conical or pear‐shaped). The first three have a clear mathematical definition, but a formula for the pyriform profile has yet to be derived. We postulate here a theoretical formula that is a universal equation solution for determining egg contours, including the pyriform.
Commercial poultry production is associated with a range of stresses, including environmental, technological, nutritional, and internal/biological ones, responsible for decreased productive and ...reproductive performance of poultry. At the molecular level, most of them are associated with oxidative stress and damages to important biological molecules. Poultry feed contains a range of feed-derived and supplemented antioxidants and, among them, vitamin E is considered as the "headquarters" of the antioxidant defense network. It is well-established that dietary supplementation of selenium, vitamin E, and carotenoids can modulate antioxidant defenses in poultry. The aim of the present paper is to present evidence related to modulation of the antioxidant capacities in poultry by vitamin E. Using 3 model systems including poultry breeders/males, semen, and chicken embryo/postnatal chickens, the possibility of modulation of the antioxidant defense mechanisms has been clearly demonstrated. It was shown that increased vitamin E supplementation in the breeder's or cockerel's diet increased their resistance to various stresses, including high polyunsaturated fatty acids (PUFA), mycotoxin, or heat stress. Increased vitamin E supplementation of poultry males was shown to be associated with significant increases in α-tocopherol level in semen associated with an increased resistance to oxidative stress imposed by various external stressors. Similarly, increased vitamin E concentration in the egg yolk due to dietary supplementation was shown to be associated with increased α-tocopherol concentration in the tissues of the developing embryos and newly hatched chicks resulting in increased antioxidant defenses and decreased lipid peroxidation. Furthermore, increased vitamin E transfer from the feed to egg yolk and further to the developing embryo was shown to be associated with upregulation of antioxidant enzymes reflecting antioxidant system regulation and adaptation. The role of vitamin E in cell signaling and gene expression as well as in interaction with microbiota and maintaining gut health in poultry awaits further investigation.
Toll-like receptors (TLRs) perform a vital role in disease resistance through their recognition of pathogen associated molecular patterns (PAMPs). Recent advances in genomics allow comparison of TLR ...genes within and between many species. This study takes advantage of the recently sequenced chicken genome to determine the complete chicken TLR repertoire and place it in context of vertebrate genomic evolution.
The chicken TLR repertoire consists of ten genes. Phylogenetic analyses show that six of these genes have orthologs in mammals and fish, while one is only shared by fish and three appear to be unique to birds. Furthermore the phylogeny shows that TLR1-like genes arose independently in fish, birds and mammals from an ancestral gene also shared by TLR6 and TLR10. All other TLRs were already present prior to the divergence of major vertebrate lineages 550 Mya (million years ago) and have since been lost in certain lineages. Phylogenetic analysis shows the absence of TLRs 8 and 9 in chicken to be the result of gene loss. The notable exception to the tendency of gene loss in TLR evolution is found in chicken TLRs 1 and 2, each of which underwent gene duplication about 147 and 65 Mya, respectively.
Comparative phylogenetic analysis of vertebrate TLR genes provides insight into their patterns and processes of gene evolution, with examples of both gene gain and gene loss. In addition, these comparisons clarify the nomenclature of TLR genes in vertebrates.
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