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LEUKOCYTOSPERMIA AND MALE INFERTILITY, WHAT IS NEW?
Ashok Agarwal, Ph.D.


The incidence of leukocytospermia ranges from 10 - 20% among infertile men. Its clinical significance in male infertility problems however, remains highly controversial.At the Urological Institute's Center for Advanced Research in Human Reproduction, Infertility and Sexual Function, our research has led us to conclude that leukocytospermia is harmful to fertility and has uncovered a previously unknown mechanism for the damage.

One suspected mechanism, which is already known, is that leukocytes produce reactive oxygen species (ROS).The polymorphonuclear neutrophils and macrophages that are the main components of seminal leukocytes can generate large quantities of ROS, overwhelming the ROS-scavenging mechanisms in seminal plasma and resulting in oxidative stress and damage to spermatozoa.

The other important mechanism that we have uncovered is that leukocytes trigger abnormal sperm themselves to release excessive levels of ROS. These data are convincing us that leukocytospermia has important prognostic value for fertility in some men and that leukocytospermia should be treated. Antibiotic therapy is important to control infection, but increasing antioxidant intake, either through diet or supplementation, might also reduce damaging ROS levels and improve fertility.

To investigate the relationship between leukocytospermia and male fertility, we examined semen specimens from 48 men attending the male infertility clinic, including 16 who had leukocytospermia and 32 who did not. Semen samples from 13 normal donors served as controls for the study. We looked at the relationship between leukocytospermia and semen quality and measured levels of sperm-derived ROS, total nonenzymatic antioxidant capacity of seminal plasma, and the extent of sperm nuclear DNA damage in infertile men with and without leukocytospermia.

Leukocytes were removed from the sperm suspensions using Dynabeads coated with anti-CD45 antibodies. A formyl- methionyl-leucyl-phenylalanine provocation test was used to exclude any residual leukocyte contamination. Levels of ROS production were determined in leukocyte-free sperm suspensions, and the residual capacity of pure sperm suspension for ROS production was assessed using phorbol 12-myristate 13-acetate (PMA). Total non-enzymatic antioxidant capacity of seminal plasma was measured by an enhanced chemiluminescence assay. Sperm nuclear DNA damage was assessed by sperm chromatin structure assay to determine the percentage of cells outside the main population (COMPa(t)) with abnormal chromatin structure.

Leukocytospermia was associated with one or more abnormalities of the classical sperm parameters in 93% (15/16) of cases. Abnormal sperm morphology was observed in 88% of leukocytospermic samples versus 47% of non-leukocytospermic samples.

Our results demonstrate a strong relationship between leukocytospermia and poor semen quality, increased damage to sperm nuclear DNA, and lowering of seminal total nonenzymatic antioxidant capacity (TAC). In addition, we found a significant correlation between leukocytospermia and increased potential for ROS production by sperm. Therefore, the contribution of leukocytes to ROS production in semen appears to include not only the direct release of ROS by these cells, but also the release of ROS by leukocyte-stimulated sperm. Such stimulation may be via direct contact or mediated by soluble products released by the leukocytes. Whether reduced antioxidants in seminal plasma from these patients is an inherent characteristic or is a consequence of utilization of these antioxidants in the process of neutralizing excess ROS is a matter for further investigation.

 
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Last Update : December 29, 2008
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