Leucocytes and intrinsic ROS production may be factors compromising sperm chromatin condensation status

Abstract

Considering that the final protection of the DNA against major assaults in terms of chromatin condensation is finalized in the epididymis, it is not known how sperm production of reactive oxygen species (ROS) and inflammatory processes can contribute to protamine deficiency that is predetermined in the testes. Therefore, this study aimed at investigating relationships between poor chromatin condensation, morphology, ROS production, DNA damage and the impact of the presence of leucocytes. In 70 patients, sperm DNA status was determined using TUNEL and chromomycin A(3) (CMA(3)) assays, and ROS-production by means of dihydroethidine. Morphology was evaluated according to strict criteria. The percentage of CMA(3)-positive spermatozoa and leucocyte concentration (r = 0.178, P = 0.0377) as well as percentage of ROS-positive spermatozoa (r = 0.3010; P = 0.012) correlated significantly. Particularly, patients with leucocyte counts >0.5 x 10(6) ml(-1) exhibited higher CMA(3) positivity. No association was found between CMA(3) positivity, TUNEL positivity and sperm morphology. While P- (poor prognosis: 0-4% normal morphology) and G-pattern (good prognosis: 5-14% normal morphology) morphology did not differ regarding chromatin condensation, P-pattern patients had a significantly higher percentage of DNA fragmentation (P = 0.0323). As oxidative stress is associated with disturbed chromatin condensation, results suggest that the idea that under-protamination of sperm DNA will automatically lead to DNA fragmentation might have to be revisited.

Cytosolic and mitochondrial ROS: which one is associated with poor chromatin remodeling?

“…and increased ROS possibly render DNA more susceptible to damage [De Iuliis et al 2009]. Henkel et al [2010] have also obtained a positive association between ROS production and CMA3+ sperm. A significant correlation between the percentage of 8-OHdG-positive sperm with under protamination and reduced mitochondrial membrane potential has been reported [De Iuliis et al 2009].…”

“…These results collectively suggest that as sperm undergo apoptosis, they become PI+. Henkel et al [2010] also assessed the relation between ROS production and DNA fragmentation using the TUNEL assay. Unlike the correlations observed between ROS production with apoptosis, they did not observe a correlation between ROS and DNA fragmentation [Henkel et al 2010].…”

“…Henkel et al [2010] also assessed the relation between ROS production and DNA fragmentation using the TUNEL assay. Unlike the correlations observed between ROS production with apoptosis, they did not observe a correlation between ROS and DNA fragmentation [Henkel et al 2010]. This difference might be due to the fact that TUNEL assesses late apoptosis, while Y1 + /PI-assesses early apoptosis.…”

“…Although controversial, it is believed that there is an association between poor chromatin remodeling and ROS production [De Iuliis et al 2009;Henkel et al 2010;Tunc et al 2009], however, the origin of the ROS is not clear.…”

Mechanisms of the harmful effects of bacterial semen infection on ejaculated human spermatozoa: potential inflammatory markers in semen

“…Although seminal leukocytes have the potential to cause oxidative stress, the intrinsic ROS production of spermatozoa themselves also leads to oxidative damage in male gametes, once it exceeds the ability of intrinsic sperm enzymatic and nonenzymatic systems to its neutralization [86,87]. Some investigators have reported stronger relationships between intrinsic than extrinsic ROS production in semen and sperm DNA integrity [49].…”