Telomeres, aging and reproduction.

Purpose Of Review: Women's fertility decay starts at the mid 30 s. However, the current delay of childbearing leads to ovarian aging and the need of assisted reproduction technologies (ART). Telomere biology is one of the main pathways involved in organismal aging.

Effects of age and oligoasthenozoospermia on telomeres of sperm and blood cells.

Research Question: How do age and normo- or oligoasthenozoospermia affect telomere length dynamics in spermatozoa and blood?

Design: Sperm and blood samples were collected from a cohort of 37 men aged 25 and under and 40 men aged 40 and over, with either normozoospermia (NZ) or oligoasthenozoospermia (OAZ). Telomere length was evaluated using quantitative fluorescence in-situ hybridization. Telomerase mRNA (TERC and TERT) and shelterin (TRF1) gene expression were analysed using quantitative real-time polymerase chain reaction.

Reproductive aging and telomeres: Are women and men equally affected?

Successful reproduction is very important for individuals and for society. Currently, the human health span and lifespan are the object of intense and productive investigation with great achievements, compared to the last century. However, reproduction span does not progress concomitantly with lifespan.

Impact of Ovarian Aging in Reproduction: From Telomeres and Mice Models to Ovarian Rejuvenation.

The trend in our society to delay procreation increases the difficulty to conceive spontaneously. Thus, there is a growing need to use assisted reproduction technologies (ART) to form a family. With advanced maternal age, ovaries not only produce a lower number of oocytes after ovarian stimulation but also a lower quality-mainly aneuploidies-requiring further complex analysis to avoid complications during implantation and pregnancy.

Fatal Necrotizing Fasciitis and Myositis in a Free-Ranging Iberian Lynx ().

A free-ranging Iberian lynx () was found dead after 16 mo of being reintroduced. On gross necropsy, necrotic areas in the left biceps femoris and intercostal muscles were identified. was isolated from both groups of muscles and was confirmed by PCR, corroborating a necrotizing myositis diagnostic.

Fertility, IVF and reproductive genetics.

Purpose Of Review: Telomere attrition and dysfunction has become a well established pathway involved in organismal aging, not only because it imposes a limitation to cell division and therefore, tissue regeneration but also because telomere homeostasis influences other pathways involved in aging. However, the implication of telomere biology in ovarian aging and fertility is barely starting to be unveiled.

Recent Findings: During the last years, mounting evidence in favor of the relationship between the accumulation of short telomeres and ovarian senescence has emerged.

Should we consider telomere length and telomerase activity in male factor infertility?

Purpose Of Review: The purpose of this review is to analyze what is known to date about the relation between telomeres and male fertility, and if it is possible for telomeres, or elements related to them, to be used as new prognostic biomarkers in fertility treatment.

Recent Findings: Cells in germ series, including spermatozoids, have longer telomeres (10-20 kb), and do not seem to undergo the shortening that takes place in somatic cells with age as they present telomerase activity. Longer telomere length found in the sperm of older fathers, influences their offspring possessing cells with longer telomere length.

Generation of mice with longer and better preserved telomeres in the absence of genetic manipulations.

Although telomere length is genetically determined, mouse embryonic stem (ES) cells with telomeres of twice the normal size have been generated. Here, we use such ES cells with 'hyper-long' telomeres, which also express green fluorescent protein (GFP), to generate chimaeric mice containing cells with both hyper-long and normal telomeres. We show that chimaeric mice contain GFP-positive cells in all mouse tissues, display normal tissue histology and normal survival.

Different telomere-length dynamics at the inner cell mass versus established embryonic stem (ES) cells.

Murine embryonic stem (ES) cells have unusually long telomeres, much longer than those in embryonic tissues. Here we address whether hyper-long telomeres are a natural property of pluripotent stem cells, such as those present at the blastocyst inner cell mass (ICM), or whether it is a characteristic acquired by the in vitro expansion of ES cells. We find that ICM cells undergo telomere elongation during the in vitro derivation of ES-cell lines.

Visualizing yeast chromosomes and nuclear architecture.

We describe here optimized protocols for tagging genomic DNA sequences with bacterial operator sites to enable visualization of specific loci in living budding yeast cells. Quantitative methods for the analysis of locus position relative to the nuclear center or nuclear pores, the analysis of chromatin dynamics and the relative position of tagged loci to other nuclear landmarks are described. Methods for accurate immunolocalization of nuclear proteins without loss of three-dimensional structure, in combination with fluorescence in situ hybridization, are also presented.

Mitotic expression of Spo13 alters M-phase progression and nucleolar localization of Cdc14 in budding yeast.

Spo13 is a key meiosis-specific regulator required for centromere cohesion and coorientation, and for progression through two nuclear divisions. We previously reported that it causes a G2/M arrest and may delay the transition from late anaphase to G1, when overexpressed in mitosis. Yet its mechanism of action has remained elusive.

Lte1, Cdc14 and MEN-controlled Cdk inactivation in yeast coordinate rDNA decompaction with late telophase progression.

The mechanism of chromatin compaction in mitosis has been well studied, while little is known about what controls chromatin decompaction in early G1 phase. We have localized the Condensin subunit Brn1 to a compact spiral of rDNA in mitotic budding yeast cells. Brn1 release and the resulting rDNA decompaction in late telophase coincided with mitotic spindle dissociation, and occurred asymmetrically (daughter cells first).

TGF-beta regulates the expression of transcription factor KLF6 and its splice variants and promotes co-operative transactivation of common target genes through a Smad3-Sp1-KLF6 interaction.

KLF6 (Krüppel-like factor 6) is a transcription factor and tumour suppressor with a growing range of biological activities and transcriptional targets. Among these, KLF6 suppresses growth through transactivation of TGF-beta1 (transforming growth factor-beta1). KLF6 can be alternatively spliced, generating lower-molecular-mass isoforms that antagonize the full-length WT (wild-type) protein and promote growth.

Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase.

Recent findings suggest important roles for nuclear organization in gene expression. In contrast, little is known about how nuclear organization contributes to genome stability. Epistasis analysis (E-MAP) using DNA repair factors in yeast indicated a functional relationship between a nuclear pore subcomplex and Slx5/Slx8, a small ubiquitin-like modifier (SUMO)-dependent ubiquitin ligase, which we show physically interact.

A cross-talk between hypoxia and TGF-beta orchestrates erythropoietin gene regulation through SP1 and Smads.

Erythropoietin (Epo) is the humoral regulator of red blood-cell production. Low oxygen tension increases the Epo levels by enhancing transcription, through the hypoxia-inducible factor (HIF)-1, a transcriptional modulator in oxygen-regulated gene expression. In the present work, a cooperative interaction between hypoxia, mediated by the HIF-1 complex, and transforming growth factor-beta (TGF-beta), mediated by Smad3/4, was revealed in the Epo gene.

Effect of pH and oxalate on hydroquinone-derived hydroxyl radical formation during brown rot wood degradation.

The redox cycle of 2,5-dimethoxybenzoquinone (2,5-DMBQ) is proposed as a source of reducing equivalent for the regeneration of Fe2+ and H2O2 in brown rot fungal decay of wood. Oxalate has also been proposed to be the physiological iron reductant. We characterized the effect of pH and oxalate on the 2,5-DMBQ-driven Fenton chemistry and on Fe3+ reduction and oxidation.

Culture conditions affecting biodegradation components of the brown-rot fungus Gloeophyllum trabeum.

To determine the liquid culture conditions under which the wood-degrading system of the brown-rot fungus Gloeophyllum trabeum is expressed, enzymes and metabolites from liquid and solid substrate cultures were characterized. Enzymes were analyzed by 2-D gel electrophoresis and also assayed. Growth conditions were varied by using liquid media containing: (1) low carbon, low nitrogen, (2) low carbon, high nitrogen, (3) high carbon, low nitrogen, or (4) high carbon, high nitrogen.