Oxidative stress and telomere length in human spermatozoa (#281)
Telomeres, the repetitive DNA at the end of the mammalian chromosomes that protect the genomic DNA, are progressively lost as a consequence of DNA replication. Therefore, telomere length (TL) is a limiting factor in the number of possible cellular divisions and the resulting lifespan of an organism. Previous studies indicate that sperm TL is the major determinant in offspring TL. Following meiosis, sperm TL has been established and any subsequent loss in TL cannot be repaired, with the potential for lifelong consequences for any resulting offspring.
The peripheral location of telomeres in the sperm nucleus makes them particularly vulnerable to attack by ROS. Moreover human spermatozoa are highly susceptible to ROS induced DNA damage, such that any form of oxidative stress post-meiosis could result in a permanent loss of sperm TL.
Human spermatozoa (n=11) were separated into high and low quality fractions using a discontinuous Percoll gradient, or into vital and non-vital populations using FACS. The resulting populations were analysed by RealTime-PCR to quantify TL. Low quality spermatozoa had significantly shorter TL (~35%) than high quality spermatozoa, and non-vital spermatozoa had significantly shorter TL (~40%) than vital spermatozoa. These observations suggest a link between sperm vitality, quality and TL.
To establish whether post-meiotic oxidative stress could result in a loss of sperm TL, spermatozoa (n=6) were exposed to arachidonic acid (a mitochondrial ROS generator) or 4-hydroxynonenal (a by-product of lipid peroxidation) for 15 min and assessed 24 h post treatment. Sperm TL was significantly reduced following these treatments, with 4-HNE exposure inducing the most severe loss.
The vulnerability of human sperm telomeres to loss upon exposure to oxidative stress has serious consequences not only for sperm DNA via a reduction in chromosomal protection, but also for the health of offspring due to reduced initial TL at fertilization.