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. TRF1 protein immunoreactivity was also evaluated using immunofluorescence. RESULTS: Mean sperm telomere length (STL) increased with age in the NZ group; older NZ men accumulated the longest telomeres (P < 0.001). In peripheral blood mononuclear cells (PBMC), mean telomere length decreased with age in NZ groups, although not reaching statistical significance. Interestingly, the younger OAZ group had the shortest mean telomere length (versus young NZ, P = 0.0081; versus old NZ, P = 0.0116; versus old OAZ, P = 0.0009) and accumulated the highest percentage of short telomeres compared with the other groups (overall P = 0.0017). Analysis of TERC and TERT mRNA expression in spermatozoa and PBMC did not show significant differences among groups. Statistically significant positive correlations were found between STL and seminal parameters in younger NZ men (P = 0.009 for sperm count and P = 0.007 for total progressive motility). Protein immunoreactivity of TRF1 in blood was not significantly different in all groups analysed. CONCLUSIONS: The OAZ group did not show the increase of STL with age that is seen in NZ individuals, suggesting that telomere length elongation mechanisms fail in OAZ patients. In PBMC, younger OAZ individuals showed significantly shorter mean telomere length, suggesting that this parameter could be a good biomarker of OAZ in younger OAZ patients. Telomerase gene and TRF1 mRNA expression and TRF1 protein immunoreactivity did not differ significantly between groups, and so these factors cannot be used as OAZ biomarkers.

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. Reproductive organs age, decreasing the levels of sexual hormones, which are protectors of health through their action on several organs of the body. Thus, this is the starting point of the organismal decay and infertility. This starting point is easily detected in women. In men, it goes under the surface, undetected, but it goes, nevertheless. Regarding fertility, aging alters the hormonal equilibrium, decreases the potential of reproductive organs, diminishes the quality of the gametes and worsen the reproductive outcomes. All these events happen at a different pace and affecting different organs in women and men. The question is what molecular pathways are involved in reproductive aging and if there is a possible halting or even reversion of the aging events. Answers to all these points will be explained in the present review.

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. Although there are different options to have a child at advanced maternal age (like donor eggs), this is not the preferred choice for most patients. Unless women had cryopreserved their eggs at a younger age, reproductive medicine should try to optimize their opportunities to become pregnant with their own oocytes, when chances of success are reasonable. Aging has many causes, but telomere attrition is ultimately one of the main pathways involved in this process. Several reports link telomere biology and reproduction, but the molecular reasons for the rapid loss of ovarian function at middle age are still elusive. This review will focus on the knowledge acquired during the last years about ovarian aging and disease, both in mouse models of reproductive senescence and in humans with ovarian failure, and the implication of telomeres in this process. In addition, the review will discuss recent results on ovarian rejuvenation, achieved with stem cell therapies that are currently under study, or ovarian reactivation by tissue fragmentation and the attempts to generate oocytes in vitro.