Abstract
Telomeres are repeat regions of DNA that cap either end of each chromosome, thereby providing stability and protection from the degradation of gene-rich regions. Each cell replication causes the loss of telomeric repeats due to incomplete DNA replication, though it is well-established that progressive telomere shortening is evaded in male germ cells by the maintenance of active telomerase. However, germ cell telomeres are still susceptible to disruption or insult by oxidative stress, toxicant exposure, and aging. Our aim was to examine the relative telomere length (rTL) in an outbred Sprague Dawley (SD) and an inbred Brown Norway (BN) rat model for paternal aging. No significant differences were found when comparing pachytene spermatocytes (PS), round spermatids (RS), and sperm obtained from the caput and cauda of the epididymis of young and aged SD rats; this is likely due to the high variance observed among individuals. A significant age-dependent decrease in rTL was observed from 115.6 (±6.5) to 93.3 (±6.3) in caput sperm and from 142.4 (±14.6) to 105.3 (±2.5) in cauda sperm from BN rats. Additionally, an increase in rTL during epididymal maturation was observed in both strains, most strikingly from 115.6 (±6.5) to 142 (±14.6) in young BN rats. These results confirm the decrease in rTL in rodents, but only when an inbred strain is used, and represent the first demonstration that rTL changes as sperm transit through the epididymis.
Highlights
The male germline is biologically unique in many ways, ranging from cellular structures to chromatin packaging and enzymatic activity
Telomere length for the outbred Sprague Dawley (SD) rats is in the range of 200–350 across spermatogenesis, while that for the inbred Brown Norway (BN) rats is shorter and has a decreased range of 115–160
One would anticipate less variance in the lengths of telomeres from an inbred than outbred strain due to decreased genetic heterogeneity, it has been proposed that inbred strains may have shorter somatic telomeres due to the increased oxidative stress and reduced evolutionary fitness [49]
Summary
The male germline is biologically unique in many ways, ranging from cellular structures to chromatin packaging and enzymatic activity. The progressive shortening of telomeres due to the end-replication problem can be mitigated by the enzyme telomerase; it maintains telomeres by the addition of new repeats. Containing both a protein (TERT) and an RNA template (TERC), the enzyme functions as a reverse transcriptase synthesizing a single strand of telomeric DNA complementary to TERC onto the. This newly synthesized telomeric DNA strand is used for lagging strand synthesis by DNA replication machinery [1]. Alternative lengthening of telomeres (ALT) by homologous recombination is another mechanism by which telomeres and subtelomeric regions are able to retain their length in the absence of active telomerase [2]
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