| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
DRZEJCZAK
A-KAKOL
CZEK*
From the * Institute of Human Genetics, Polish
Academy of Sciences, Pozna
, Poland; and
Clinic of Infertility and Reproductive
Endocrinology, School of Medicine, Pozna, Poland.
| Correspondence to: Prof Maciej Kurpisz, Institute of Human Genetics, Polish
Academy of Sciences, Strzeszyska 32, Pozna, Poland (e-mail:
kurpimac{at}man.poznan.pl) |
| Received for publication May 16, 2002; accepted for publication November 19, 2002. |
 |
Abstract |
|---|
 Top Abstract Materials and MethodsResultsDiscussionReferences |
|---|
[TNF])
detectable in seminal plasma during male genital tract inflammation could be
considered as mediators between altered semen parameters and changed levels of
pro-oxidant and antioxidant substances. Studies using chemiluminometric,
spectrophotometric, and enzyme-linked immunosorbent assay methods indicate
that proinflammatory cytokines such as IL-1ß, IL-6, IL-8, and TNF
may modulate pro-oxidant and antioxidant activities in the male genital tract.
The data also suggest that the function of pro-oxidant and antioxidant systems
in semen may directly influence basic semen parameters. The elevated numbers
of leukocytes present in semen during male genital tract inflammation without
an associated contribution of cytokines and semen antioxidant capacity appear
to be of little prognostic value in evaluating male fertilization
potential.
Key words: Semen, leukocytes, reactive oxygen species, infertility, cytokines
Activation of seminal plasma white blood cells during genital tract inflammation or cellular reactions against microbial antigens may trigger the release of a variety of products such as proteolytic enzymes, cytokines, and reactive oxygen species (ROS). A negative association between excessive ROS production and human male fertility has been demonstrated in a range of earlier studies (de Lamirande and Gagnon, 1992; Griveau et al, 1995; Kurpisz et al 1996; Sanocka et al, 1996; Ochsendorf, 1999; Pasqualotto et al, 2001).
A detrimental leukocyte influence on egg fertilization has been documented (Miesel et al, 1993; Vicino et al, 1999) and it is quite possible that such a negative effect was caused either by cytokines or ROS generated by white blood cells.
Some authors have suggested that limited amounts of ROS are essential for
the induction of physiological mechanisms such as capacitation and the
acrosome reaction of human sperm (Zini et
al, 1995; de Lamirande and
Gagnon, 1997; de Lamirande et
al, 1997). Hence, ROS generation under the precise control of the
antioxidant system must be considered as an important factor for sperm
function and to play a role in signal transduction
(Joseph and Cutler, 1994). It
is still not clear whether some leukocyte contamination may have a positive
influence on sperm function and which factors would change this effect. By
observing molecular mechanisms of infertility it has been recently speculated
that cytokines and their soluble receptors have a close relationship with male
infertility and sperm function at particular steps of the reproduction process
(Buch et al, 1994; Huleihel et
al, 1996,
1999;
Denison et al, 1999;
Matalliotakis et al, 2000). Proinflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6),
interleukin-8 (IL-8), and tumor necrosis factor- (TNF-) have
been scrutinized in studies because the inflammation process is usually
associated with their presence, and as a consequence, stimulates antioxidant
feedback (Rajasekaran et al,
1995).
In order to evaluate the influence of cytokines, ROS, and enzymatic
pro-oxidants and antioxidants on the fertility potential, we undertook
measurements of selected cytokines (IL-1ß, IL-6, IL-8, and TNF) in
seminal plasma samples obtained from healthy individuals and men with genital
tract inflammation; pro-oxidant and antioxidant enzymatic substances and basic
seminological features (including leukocytes) in infected semen samples and in
semen from healthy, uninfected subjects; and attempted to demonstrate possible
interconnections between the measured substances and semen parameters in both
assessed populations of men (with and without genital tract inflammation).
|
Materials and Methods |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Hospital College. In this group of patients, semen was
normozoospermic according to an assessment of sperm density (>20 million/mL
of ejaculate). Leukocyte numbers in the semen of these individuals always
exceeded >0.5 x 106 cells/mL of ejaculate and
bacteriological screening indicated the presence of pathological bacterial
strains (>103 bacteria/mL). In some ejaculated samples of this
group, leukocytes exceeded 1 x 106/mL of ejaculate with or
without the presence of pathological flora. Female partners were carefully
examined for anatomical, hormonal, and immunological parameters, however,
normal ovulatory profiles, patent fallopian tubes, and no signs of
immunological reactions to gametes were detected. We assigned these couples as
idiopathically infertile on the basis of their infertility lasting at least 2
years.
Sperm Preparations
After 30 minutes of semen liquefaction at room temperature, semen samples
were subjected to the routine andrological analysis (semen volume, sperm and
leukocyte densities, progressive motility, morphology, and viability).
Spermatozoa from all examined samples were separated from seminal plasma by
centrifugation at 300 x g for 10 minutes and at 500 x
g in special cases when problems with semen viscosity occurred.
Plasma samples were then used to determine superoxide dismutase, catalase,
gluthathione peroxidase, xanthine oxidase, and interleukin concentrations.
Chemicals and Equipment
Unless otherwise stated, all reagents used to determine enzymatic
pro-oxidants and antioxidants were purchased from Sigma-Aldrich (Steinheim,
Germany), except xanthine oxidase, which was purchased form Fluka Chemie
(Buchs, Switzerland). Reagents for determining interleukin levels were
purchased from Genzyme Corporation (Cambridge, Mass).
All chemiluminometric assays were performed using Luminometer Berthold LB953 (EG and Berthold, Bad Wildbad, Germany).
Superoxide Dismutase
Superoxide dismutase (SOD) activity was quantified by chemiluminescence
(Miesel and Weser; 1991; Miesel and Haas, 1993) using
the xanthine/xanthine oxidase lucigenin assay. A final volume of 1 mL of the
sample contained the following components: 100 µL of seminal plasma, 100 mM
diethylenetriaminepentaacetic acid (DTPA), 100 mM lucigenin, 180 nM xanthine
oxidase, and 50 mM xanthine in 50 nM HEPES (pH 7.4). The addition of xanthine
started the reaction and the resulting photon emission was recorded in a
Berthold LB 953 luminometer at 25°C. Bovine SODCuZn was used for
calibration. One unit represented the concentration of SOD required to inhibit
the release of superoxide by 50% and equals 5 nM copper.
Catalase
Catalase activity was determined chemiluminometrically
(Aebi, 1974) in the presence of
luminol. The initial enzymatic decomposition of hydrogen peroxide is the
first-order reaction at low concentrations of hydrogen peroxide (less than 10
nM), and is directly proportional to the concentration of substrate and the
concentration of enzyme. One milliliter contained 100 mM luminol, 100 mM DTPA,
5 mM H2O2, and 20 µL of seminal plasma. The reaction
commenced with the addition of H2O2. The resulting
chemiluminescence was recorded for 3 minutes in a Berthold LB 953 luminometer
at 25°C. Chromatographically purified catalase from bovine liver was used
for calibration. One unit of catalase decomposes 1.0 mM
H2O2 per minute under specified conditions.
Glutathione Peroxidase
Glutathione peroxidase activity was determined by spectrophotometric assay
as described by Flohe and Gunzler
(1984) and Rice-Evans et al
(1991). The following reagents
were used: 0.1 M potassium phosphate buffer (pH 7.0) containing 0.1 mM
ethylenediamine tetraacetic acid (EDTA), 2.4 U/mL glutathione reductase, 10 mM
reduced glutathione (GSH) in water, 1.5 mM NADPH in 0.1% NaHCO3, 12
mM t-butylhydroperoxide, 1.5 mM H2O2 in water.
Test enzyme samples contained 0.05–1.0 U/mL. The following reagents were
pipetted into a semimicrocuvette set at 37°C: 500 µL of 0.1 M phosphate
buffer (pH 7.0), 100 µL of seminal plasma sample, 100 µL of glutathione
reductase (0.24 U); and 100 µL of 10 mM glutathione solution. The
H2O2-independent oxidation of NADPH was measured for 3
minutes in order to give a baseline at 340 nm. The reaction began with the
addition of 100 µL of a solution of either t-butylhydroperoxide or
1.5 mM H2O2 that had been prewarmed to 37°C. The
decrease in absorbance was monitored for 5 minutes. Replacing the glutathione
peroxidase-containing sample with the buffer enabled an assessed the
nonenzymatic reaction.
Xanthine Oxidase
The xanthine oxidase activity was determined by the chemiluminometric assay
described by Miesel and Weser
(1991) and Rice-Evans et al
(1991) with application of
xanthine. A final volume of a 1-mL sample contained the following mixture: 100
µL of seminal plasma, 10 mM DTPA, 100 mM lucigenin, and 50 mM xanthine in
50 mM HEPES (pH 7.4). The addition of xanthine initiated the reaction and the
resulting photon emission was recorded in a Berthold LB 953 luminometer at
25°C.
Interleukin-1ß, Interleukin-6, Interleukin-8, TNF
The Predicta (Cambridge, MA) IL-1ß, IL-6, IL-8, and TNF enzyme
immunoassay kits contain a 96-well microtiter plate precoated with monoclonal
antibody to a proper cytokine. A measured volume of the studied samples,
either standard substance or control buffer, was added to each test well and
incubated to allow any cytokine present to be captured by antibodies on the
microtiter plate. The wells were then washed, and a biotin-labeled polyclonal
antibody to the tested cytokine was added to bind the captured IL-1ß,
IL-6, IL-8, or TNF. The wells were washed again and a
peroxidase-labeled avidin reagent was added to attach the biotin (in the
immune complex) on the plate. After incubation the wells were washed and a
peroxidase-labeled goat anti-rabbit immunoglobulin G was added to attach the
polyclonal antibody (in the immune complex) on the plate. After a third wash,
a substrate buffer (peroxide) and chromogen (tetramethylbenzidine) were added
to the wells, thereby producing a blue color in the presence of peroxidase.
The color reaction was stopped by the addition of sulfuric acid, which
converted the blue color to yellow. The intensity of the colorimetric
reactions was in a direct proportion to the amount of tested cytokine present
in the studied sample or standard. The absorbance was read with Multiscan Plus
(Labsystems, Helsinki, Finland) at 450 nm, and a standard curve was
constructed to quantitate cytokine concentrations.
Respective values for detection limit, reproducibility range, and source of antibodies are as follows:
Human IL-1ß: detection limit, 3 pg/mL; intra-assay value, 8.2%; interassay value, 9.6%; source of antibody, biotinylated rabbit anti-human (Yang et al, 1993);
Human IL-6: detection limit, 18 pg/mL; intra-assay value, 6.6%; interassay value, 8.8%; source of antibody, biotinylated rabbit anti-human (Wong et al, 1988);
Human IL-8: detection limit, 1 pg/mL; intra-assay value, 6.6%; inter-assay value, 11%; source of antibody, biotinylated rabbit anti-human (Gesser et al, 1996);
Human TNF: detection limit, 3 pg/mL; intra-assay value, 6%;
inter-assay value, 10%; source of antibody, biotinylated rabbit anti-human
(Braegger et al, 1992).
Undiluted antibodies were applied in the all cases (no titration therefore was performed).
Statistical Analysis
The results are presented as a median. The statistical significance of the
results was assessed using the Kruskal-Wallis nonparametric analysis of
variance test, the Mann-Whitney U-test, and Spearman rank order
correlations.
|
Results |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
|
Catalase in Seminal Plasma
Median catalase seminal plasma levels obtained in a cohort of healthy
donors was 4.3 U/mL x 103. In a group of men with infertility
and genital tract inflammation, the activity of catalase presented as a median
was 3.0 U/mL x 103. This difference was found to be
statistically significant (P < .05, see
Table 1).
Glutathione Peroxidase in Seminal Plasma
Seminal plasma samples from healthy controls (n = 22) presented as a median
of 5.5 U/mL x 10-3 of glutathione peroxidase. In
men with infertility and genital tract inflammation, the activity of
glutathione peroxidase was elevated; the median was 6.5 U/mL x
10-3. The difference was not statistically significant
(P = .1, see Table
1).
Xanthine Oxidase in Seminal Plasma
Xanthine oxidase activity was elevated in a group of men with infertility
and semen inflammation (median 8.01 U/mL x 10-3)
in comparison with that of healthy controls (median 3.25 U/mL x
10-3). This difference was found to be statistically
significant (P < .01, see Table
1).
IL-1ß in Seminal Plasma
Seminal plasma from healthy individuals contained IL-1ß with a median
value of 10.0 pg/mL. Seminal plasma samples from normozoospermic but infertile
men with genital tract inflammation contained clearly elevated levels of
IL-1ß compared with that of controls (median 155.0 pg/mL). This
difference was found to be statistically significant (P < .05, see
Table 1).
IL-6 in Seminal Plasma
Seminal plasma from healthy, normozoospermic controls contained moderate
levels of IL-6 at a median of 10.5 pg/mL. However, seminal plasma samples from
patients with genital tract inflammation contained very high IL-6 levels with
a median value of 107.5 pg/mL, which was considered to be statistically
significant (P < .001, see
Table 1).
IL-8 in Seminal Plasma
Concentrations of IL-8 in seminal plasma of normozoospermic men with
infertility and genital tract inflammation (median 1100.0 pg/mL) was
significantly different from values detected in seminal plasma samples of
healthy men (median 575.0 pg/mL, P < .05, see
Table 1).
TNF in Seminal Plasma
TNF was detectable in seminal plasma samples obtained from healthy
men, with a median value of 6.5 pg/mL. Higher concentrations of this cytokine
(median value 8.0 pg/mL) was observed in a group normozoospermic infertile men
with genital tract inflammation, although it was not statistically significant
(P > .05, see Table
1).
Oxido-Sensitive Index
The Oxido-sensitive index (SOD/xanthine oxidase) of seminal plasma was also
determined according to our previous observation, indicating the importance of
balance between pro-oxidant and antioxidant enzymatic substances
(Kurpisz et al, 1996). On
average, the oxido-sensitive index in ejaculated samples from healthy controls
(1.11) was higher than in samples from infertile men (0.45) with genital tract
inflammation, and the difference was statistically significant (P
< .01, Table 1). A
diminished oxido-sensitive index value may indicate that pro-oxidant activity
overwhelms antioxidant protection with respective consequences (eg,
peroxidation of lipids) for sperm membranes (plasmalemma dysfunction).
Semen Parameters
The seminological parameters determined in samples from patients with
genital tract infection (sperm density, progressive motility, nonprogressive
motility, morphology, and viability) differed from those in semen from healthy
controls, however, statistical significance was observed in sperm density,
progressive motility, and morphology (Table
2).
|
Spearman Rank Order Correlation Among Semen Parameters, Antioxidant
and Pro-Oxidant Activities, and Concentration of Studied Cytokines
In seminal plasma from healthy donors we observed only one correlation that
occurred between xanthine oxidase and catalase (r = -.599, P
= .018, Table 3), whereas there
were as many as six statistically significant (P < .05)
correlations in seminal plasma from infertile men with genital tract
inflammation; of these, 2 were positive
(Table 3). These correlations
indicate the relationship between the studied cytokines and pro-oxidant and
antioxidant substances as well as pro-oxidant and antioxidant enzymes and
measured seminological parameters. When the examined individuals (n = 61) were
analyzed statistically (Table
4), the range of the observed correlations was extended and
reached more than 20 significant correlations. Of those, 7 were positive and
11 were negative (although the general nature of correlations was similar to
the one revealed in a subgroup of infertile men with genital tract
inflammation). It should be further emphasized that elevation of xanthine
oxidase was always associated with a deterioration of sperm parameters,
where-as proinflammatory cytokines up-regulated xanthine oxidase
(Table 4). On the other hand,
in a group of studied individuals, catalase usually has been negatively
associated with IL-1ß, IL-6, IL-8, and TNF (Tables
3 and
4). Low catalase activity can
be associated with low semen quality (sperm density and progressive motility),
as can be implied from Table 4.
This noted appropriately in the
Figure.
|
|
|
|
Discussion |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
seem to modulate the
activity of pro-oxidant and antioxidant enzymes and can severely influence
basic semen parameters. Of all the cytokines analyzed in this experimental
design, IL-1ß, IL-6, and IL-8 were statistically significant indicators
of pathological process in semen (Table
1). Leukocytic infiltration into the human ejaculate is believed to be a clinically significant factor in the etiology of infertility (Aitken et al, 1999). Existing controversies in recent literature do not sufficiently emphasize the role of genital tract inflammation in transient or persistent male infertility.
In our previous studies (Kurpisz et al 1996; Sanocka et al, 1996; Miesel et al 1997) we suggested that a non-equilibrated antioxidant system in semen might be one of the important reasons for these conflicting results. When a general antioxidant capacity of semen (total trapping) is characterized, a fundamental change in the action of particular enzymatic factors in semen can be omitted (Sanocka et al 1997).
A study by Aitken et al (1999) postulated that leukocyte infiltration (to the point of leukocytospermia >1 x 106/mL of semen) had no influence on the morphology of sperm cells or their motility. On the other hand, a profound influence of the leukocytes on the functional capacity of the washed sperm preparations at the stage of sperm-oocyte fusion was observed. In general, whenever leukocytes were added to the purified gametes, a sperm-oocyte fusion cannot occur. The ROS threshold of ROS generation influencing sperm-oocyte fusion was previously presented (Miesel et al, 1993). On the other hand, Tomlinson et al (1993) suggested that measurement of seminal plasma leukocytes in a routine semen analysis appeared to be of little prognostic value in male fertilization potential. Furthermore, these authors postulated that elevated concentrations of neutrophils and macrophages improved sperm morphology and semen density. Those results are outwardly incompatible with our observations because an efficient antioxidant system is sometimes able to scavenge even very high amounts of ROS. Therefore, both arms of the equation (pro-oxidants and antioxidants) must be carefully analyzed.
Genital tract inflammation reflected in leukocytospermia must certainly enhance the levels of free radicals, and its effects on semen parameters might be strictly dependent on initial antioxidant capacity. It is not a surprise that a comparison of leukocytospermic samples (1 x 106/mL of semen) with nonleukocytospermic samples revealed significant differences at the levels of ROS, however, the antioxidant status was not precisely characterized (Tomlinson et al, 1993). In another study (Kessopoulou et al, 1992), the authors did not find a significant correlation between sperm morphology and ROS; only the beat cross-frequency of the sperm tail was negatively correlated with ROS levels. In our previous studies (Kurpisz et al, 1996; Sanocka et al, 1996; Miesel et al, 1997) we demonstrated that an inefficient semen antioxidant system correlated with infertility and semen pathology, and was especially associated with asthenozoospermia. Furthermore, we observed that elevated levels of peroxidated lipids in the cell membranes of spermatozoa hinted at significant generation of ROS (Sanocka et al, 1997).
A study by Leib et al (1994) examined a relationship between chronic abacterial prostatitis and the development of male infertility. Statistical evaluation of these 2 groups, normal fertile men and patients with longstanding (1–20 years) chronic abacterial prostatitis, showed that sperm motility parameters, sperm morphology, prostate markers, and white blood cells were out of the normal range in the group with chronic, abacterial prostatitis. In addition, a correlation was found between the duration of the disease and 2 important semen variables: increased prostatic markers and appearance of sperm morphological defects. Furthermore, the authors suggested that the other reasons for such observed pathological symptoms could be linked to persistent generation of ROS in semen of patients with nonbacterial inflammation. During genital tract inflammation, beside leukocyte contamination, quite often (but not always), pathological bacterial strains may appear in semen. Hence, another group of authors concentrated mainly on bacterial semen infections and its relation to infertility (Monga and Roberts, 1994; Merino et al, 1995; Keck et al, 1998; Potts et al, 2000) and indicated that bacterial infections might cause visible alterations in semen characteristics, volume, sperm motility, and viability. Immobilization or death of spermatozoa can be a biological response to the action of bacterial toxins. The influence of genital inflammation on fertility was mediated through diminished sperm motility due to the adherence of dialyzable factors in semen samples (Monga and Roberts, 1994).
Our results point to another mechanism of male infertility. In this hypothetical situation, pathological bacterial strains present in semen (even without contaminating leukocytes) may cause an increase of cytokine levels that in turn may abolish the activity of catalase and up-regulate the xanthine oxidase action (see the Figure). Those changes are the direct consequence of exposure to ROS (in what may create a vicious circle), progressively exhausting the antioxidant scavenging capacity and thereby impairing the membrane structures of spermatozoa.
We believe that the crucial role in perpetuation of the inflammatory process may belong to cytokines, and that these bioactive substances may constitute an important link between inflammation and male infertility. Cytokines released by various cell populations can be involved in proliferative and differentiating responses of a variety of cell subsets (including germ cells) and are capable of markedly influencing the biological activities of these cells (Fedder, 1996; Dousset et al, 1997).
In addition, proinflammatory cytokines such as: IL-1ß, IL-6, and
TNF are involved in the reduction of the ability of spermatozoa to
penetrate. Grushwitz et al
(1996) determined the cytokine
content in seminal plasma of patients with unexplained infertility and
correlated these results with urogenital infections and sperm parameters. They
observed that IL-1ß, IL-6, and TNF levels in seminal plasma were
negatively correlated with the number of progressively motile sperm, but there
was no correlation with a total sperm count, viability, pH, morphological
sperm abnormalities, or hormonal parameters. Cytokine levels (seminal plasma)
were significantly elevated, indicating bacterial or mycoplasmal infections of
the urogenital tract. Fedder and Ellermann-Ericsen
(1995) more closely
investigated the effect of cytokines TNF, IL-8, and IFN-
on
sperm motility and the acrosome reaction. Among the cytokines examined, only
IFN- showed an ability to inhibit sperm motility, and this phenomenon
was observed only when high concentrations of the cytokine were applied.
Sikka et al (2001) in their
study suggested that combinations of lipopolysaccharides and
interferon- are detrimental to human spermatozoa and may contribute to
male infertility in patients with chronic genitourinary inflammation. In the
present study, we have strongly indicated that the activity of the antioxidant
system is dependent on particular interleukins (Tables
3 and
4), which can be potent
modulating factors of antioxidant semen capacity. A clear relationship between
basic semen parameters and oxidative stress was well observed.
It has been recently established that ROS may act as intracellular
signaling molecules to mediate the biological effects of cytokines. One of the
main targets of ROS is transcription factor 
B (nuclear factor-B
[NFB]). NFB-dependent transcription is inhibited by antioxidants
and its activation is induced or potentiated by ROS
(Boulares et al 2000;
Bowie et al 2000;
Kwon et al, 2000). It has been
known that TNF may increase IL-6 gene expression through the activation
of NFB, and that the antioxidants can suppress TNF-dependent
IL-6 expression, thereby inhibiting the activation of the transcriptionally
active NFB (Kikumori et al,
1998).
The precise molecular mechanisms for regulating the antioxidant response to male genital tract inflammation remains unclear, however, results generated so far indicate that cytokines may play an important role during the inflammatory reactions and are connected with oxidative metabolism.
In summary, we provide further evidence that 1) proinflammatory cytokines
such as IL-1ß, IL-6, IL-8, and TNF modulate pro-oxidant and
antioxidant activities; 2) the function of pro-oxidant and antioxidant systems
in semen may directly influence semen parameters and that long-term genital
tract inflammations may lead to male infertility; 3) measurement of seminal
plasma leukocytes during male genital tract inflammation without an associated
contribution of cytokines or semen antioxidant capacity appears to have little
prognostic value in the evaluation of male fertilization potential. Taking
into account the results presented, it should be considered the application of
selected antioxidants in supplementary treatments for men with genital tract
inflammations.
|
Footnotes |
|---|
|
References |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Aitken RJ, Irvine DS, Wu FC. Prospective analysis of sperm-oocyte fusion and reactive oxygen species generation as criteria for the diagnosis of infertility. Am J Obstet Gynecol.1991; 164:542 –551.[Medline]
Aitken RJ, West K, Buckingham D. Leukocytic infiltration into human ejaculate and its association with semen quality, oxidative stress, and sperm function. J Androl.1999; 15:343 –352.
Arata de Bellabarba G, Tortolero I, Villarroel V, Molina CZ, Bellabarba C, Velasquez E. Nonsperm cells in human semen and their relationship with semen parameters. Arch Androl.2000; 45:131 –136.[Medline]
Boulares AH, Giardina C, Inan MS, Khairallah EA, Cohen SD.
Acetaminophen inhibits NF-kappa B activation by interfering the oxidant signal
in murine Hepa 1–6 cells. Toxicol Sci.2000; 55:370
–375.
Bowie AG, O'Neill LA. Vitamin C inhibits NF-kappa B activation by
TNF via the activation of p38 mitogen-activated protein kinase. J
Immunol. 2000;165:7180
–7178.
Braegger CP, Nicholls S, Murch SH, Stephens S, MacDonald TT. Tumour necrosis factor alpha in stool as a marker of intestinal inflammation. Lancet. 1992;339:89 –91.[Medline]
Buch JP, Kolon TF, Maulik N, Kreutzer DL, Das DK. Cytokines stimulate lipid membrane peroxidation of human sperm. Fertil Steril. 1994;62:186 –188.[Medline]
de Lamirande E, Gagnon C. Reactive oxygen species and human spermatozoa. I. Effects on the motility of intact spermatozoa and sperm axonemes. J Androl.1992; 16:21 –25.
de Lamirande E. Gagnon C. Capacitation as a regulatory event that
primes spermatozoa for the acrosome reaction and fertilisation. Mol
Hum Reprod. 1997;3:175
–193.
de Lamirande E, Jiang H, Zini A, Kodama H, Gagnon C. Reactive oxygen species and sperm physiology. Rev Reprod.1997; 2:48 –54.[Abstract]
Denison FC, Grant VE, Calder AA, Kelly RW. Seminal plasma
components stimulate interleukin-8 and interleukin-10 release. Mol
Hum Reprod. 1999;5:220
–226.
Dousset B, Hussenet F, Daudin M, Bujan L, Foliguet B, Nabet P.
Seminal cytokine concentrations (IL-1-beta, IL-2, IL-6, sR IL-2, sR IL-6),
semen parameters and blood hormonal status in male infertility. Hum
Reprod. 1997;12:1476
–1479.
Fedder J. Nonsperm cells in human semen: with special reference to seminal leukocytes and their possible influence on fertility. Arch Androl. 1996;36:41 –65.[Medline]
Fedder J, Askjaer SA, Hjort T. Nonspermatozoal cells in semen: relationship to other semen parameters and fertility status of the couple. Arch Androl.1993; 31:95 –103.[Medline]
Fedder J, Ellermann-Ericsen S. Effect of cytokines on sperm motility and ionophore-stimulated acrosome reaction. Arch Androl. 1995;35:173 –185.[Medline]
Flohe L, Gunzler WA. Assays of glutathione peroxidase. Methods Enzymol.1984; 105:114 –121.[Medline]
Gesser B, Lund M, Lohse N, Vestergaad C, Matsushima K, Sindet-Pedersen S, Jensen SL, Thestrup-Pedersen K, Larsen CG. IL-8 induces T cell chemotaxis, suppresses IL-4, and up-regulates IL-8 production by CD4+ T cells. J Leukoc Biol.1996; 59:407 –411.[Abstract]
Griveau JF, Dumont E, Renerd P. Reactive oxygen species, lipid peroxidation, and enzymatic defence systems in human spermatozoa. J Reprod Fertil. 1995;103:17 –26.
Gruschwitz MS, Brezinschek R, Brezinschek HP. Cytokine levels in the seminal plasma of infertile males. J Androl.1996; 14:158 –163.
Huleihel M, Lunenfeld E, Horowitz S, Levy A, Potashnik G, Mazor M, Glezerman M. Expression of IL-12, IL-10, PGE2, sIL-2R and sIL-6R in seminal plasma of fertile and infertile men. Andrologia.1999; 31:283 –288.[Medline]
Huleihel M, Lunenfeld E, Levy A, Potashnik G, Glezerman M. Distinct expression levels of cytokines and soluble cytokine receptors in seminal plasma of fertile and infertile men. Fertil Steril.1996; 66:135 –139.[Medline]
Joseph JA, Cutler RC. The role of oxidative stress in signal transduction changes and cell loss in senescence. Ann N Y Acad Sci. 1994;738:37 –43.[Medline]
Keck C, Gerber-Schafer C, Clad A, Wilhelm C, Breckwoldt M. Seminal
tract infections: impact on male fertility and treatment options.
Hum Reprod Update.1998; 4:891
–903.
Kessopoulou E, Tomlinson MJ, Barrat CRL, Bolton AE, Cooke ID. Origin of reactive oxygen species in human semen: spermatozoa or leukocytes? J Reprod Fertil.1992; 94:463 –470.
Kikumori T, Kambe F, Nagaya T, Imai T, Funahashi H, Seo H.
Activation of transcriptionally active nuclear factor-kappa B by tumour
necrosis factor-alpha and its inhibition by antioxidants in rat thyroid FRTL-5
cells. Endocrinology.1998; 139:1715
–1722.
Kurpisz M, Miesel R, Sanocka D, JeEdrzejczak P. Seminal
plasma can be a predictive factor for male infertility. Hum
Reprod. 1996;11:1223
–1226.
Kwon HJ, Kang MJ, Kim HJ, Choi JS, Paik KJ, Chung HY. Inhibition of NF kappa B by methyl chlorogenate from Eirob japonica. Mol Cells. 2000;10:241 –246.[Medline]
Leib Z, Bartoov B, Eltes F, Servadio C. Reduced semen quality caused by chronic abacterial prostatitis: an enigma or reality? Fertil Steril.1994; 61:1009 –1116.
Mankveld R, Kruger TF. Sperm morphology and male urogenital infections. Andrologia.1998; 30:49 –53.
Matalliotakis I, Goumenou A, Fragouli Y, Matalliotakis G, Kyriakou D, Koumantakis E. Soluble IL-6 receptor levels in the seminal plasma of infertile patients with accessory gland infection. Arch Androl. 2000;44:237 –242.[Medline]
Merino G, Carranze-Lira S, Murrieta S, Rodriguez L, Cuevas E, Moran C. Bacterial infection and semen characteristics in infertile men. Arch Androl.1995; 35:43 –47.[Medline]
Miesel R, Haas R. Reactivity of an active centre analog of Cu2Zn2 superoxide dismutase in murine model of acute and chronic inflammation. Inflammation.1993; 17:595 –611.[Medline]
Miesel R, JeEdrzejczak PJ, Kurpisz M. Oxidative stress during the interaction of gametes. Biol Reprod.1993; 49:918 –923.[Abstract]
Miesel R, JeEdrzejczak P, Sanocka D, Kurpisz M. Severe antioxidase deficiency in human semen with pathological spermiogram parameters. Andrologia.1997; 29:77 –83.[Medline]
Miesel R, Weser U. Chemiluminiscence assays of Cu2Zn2 superoxide dismutase mimicking the effect of cytokines: Cu-complexes. Free Rad Res.1991; 12–13:253 –258.
Monga M, Roberts JA. Spermagglutination by bacteria,
receptor-specific interactions. J Androl.1994; 15:151
–156.
Naz RK, Chaudhry A, Witkin SS. Lymphocyte proliferative response to fertilisation antigen in patients with antisperm antibodies. Am J Obstet Gynecol. 1990;18:161 –177.
Ochsendorf FR. Infections in the male genital tract and reactive
oxygen species. Hum Reprod Update.1999; 5:399
–420.
Pasqualotto FF, Sharma RK, Kobayashi H, Nelson DR, Thomas AJ Jr, Agarwal A. Oxidative stress in normospermic men undergoing infertility evaluation. J Androl.2001; 22:316 –322.[Abstract]
Potts RJ, Notarianni LJ, Jefferies TM. Seminal plasma reduces exogenous oxidative damage to human sperm, determined by the measurement of DNA strand breaks and lipid peroxidation. Mutat Res.2000; 447:249 –256.[Medline]
Rajasekaran M, Hellstrom WJ, Naz RK, Sikka SC. Oxidative stress and interleukins in seminal plasma during leukocytospermia. Fertil Steril. 1995;64:166 –171.[Medline]
Rice-Evans CA, Diplock AT, Symons MCR. Techniques in free radical research. Amsterdam: Elsevier; 1991:194 –196, 201–202.
Sanocka D, Miesel R, JeEdrzejczak P,
Chemoska-Soyta A, Kurpisz M. Effect of reactive oxygen species
and the activity of antioxidant systems on human semen; association with male
infertility. Int J Androl.1997; 20:255
–264.
Sanocka D, Miesel R, JeEdrzejczak P, Kurpisz M. Oxidative
stress and male infertility. J Androl.1996; 17:449
–454.
Sikka SC, Champion HC, Bivalacqua TJ, Estrada LS, Wang R, Rajasekaran M, Aggarwal BB, Hellstrom WJ. Role of genitourinary inflammation in infertility: synergistic effect of lipopolysaccharide and interferon-gamma on human spermatozoa. Int J Androl.2001; 24:136 –141.[Medline]
Tomlinson MJ, Barrat CLR, Cooke ID. Prospective study of leukocytes and leukocyte subpopulations in semen suggests they are not a cause of male infertility. Fertil Steril.1993; 60:1069 –1076.[Medline]
Vicino M, Loverro G, Simonetti S, Mei L, Selvaggi L. The correlation between idiopathic leukocytospermia, embryo quality and outcome in the FIVET and ICSI procedures. Minerva Gynecol.1999; 51:413 –420.[Medline]
Wolff H. The biologic significance of white blood cells in semen. Fertil Steril.1995; 63:1143 –1157.[Medline]
Wong GG, Witek-Giannotti JS, Temple PA, et al. Stimulation of murine hemopoietic colony formation by human IL-6 [abstract.] J Immunol. 1988;140:3040 –3044.[Abstract]
World Health Organization. Laboratory Manual for the Examination of Human Semen and Semen-Cervical Mucus Interaction. 3rd ed. Cambridge, UK: Cambridge University Press;1992 .
Yang F, Jansen L, Friedrichs WE, Buchanan JM, Bowman BH. IL-1 beta decreases expression of amyloid precursor protein gene in human glioma cells. Biochem Biophys Res Commun.1993; 191:1014 –1019.[Medline]
Zalata AA, Christophe AB, Depuydt CE. White blood cells cause oxidative damage to the fatty acid composition of phospholipids of human spermatozoa. Int J Androl.1998; 21:154 –162.[Medline]
Zini A, de Lamirande E, Gagnon C. Low levels of nitric oxide
promote human sperm capacitation in vitro. J Androl.1995; 16:424
–431.
This article has been cited by other articles:
|
|
 |
|
  K. Tremellen Oxidative stress and male infertility--a clinical perspective Hum. Reprod. Update, May 1, 2008; 14(3): 243 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fraczek, D. Sanocka, M. Kamieniczna, and M. Kurpisz Proinflammatory Cytokines as an Intermediate Factor Enhancing Lipid Sperm Membrane Peroxidation in In Vitro Conditions J Androl, January 1, 2008; 29(1): 85 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Politch, L. Tucker, F. P. Bowman, and D. J. Anderson Concentrations and significance of cytokines and other immunologic factors in semen of healthy fertile men Hum. Reprod., November 1, 2007; 22(11): 2928 - 2935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Brackett, D. R. Cohen, E. Ibrahim, T. C. Aballa, and C. M. Lynne Neutralization of Cytokine Activity at the Receptor Level Improves Sperm Motility in Men With Spinal Cord Injuries J Androl, September 1, 2007; 28(5): 717 - 721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Forges, P. Monnier-Barbarino, J.M. Alberto, R.M. Gueant-Rodriguez, J.L. Daval, and J.L. Gueant Impact of folate and homocysteine metabolism on human reproductive health Hum. Reprod. Update, May 1, 2007; 13(3): 225 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fraczek and M. Kurpisz Inflammatory mediators exert toxic effects of oxidative stress on human spermatozoa J Androl, March 1, 2007; 28(2): 325 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Leslie, H. J. Lachmann, E. Bruning, J. A. McGrath, A. Bybee, J. R. Gallimore, P. F. Roberts, P. Woo, C. E. Grattan, and P. N. Hawkins Phenotype, Genotype, and Sustained Response to Anakinra in 22 Patients With Autoinflammatory Disease Associated With CIAS-1/NALP3 Mutations Arch Dermatol, December 1, 2006; 142(12): 1591 - 1597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Cohen, S. Basu, J. M. Randall, T. C. Aballa, C. M. Lynne, and N. L. Brackett Sperm Motility in Men With Spinal Cord Injuries Is Enhanced by Inactivating Cytokines in the Seminal Plasma J Androl, November 1, 2004; 25(6): 922 - 925. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
