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Effects of Dietary Selenium on Sperm Motility in Healthy Men

Authors:

Abstract

A deficiency of dietary selenium leads to immotile, deformed sperm and infertility in rats, whereas supplementation of the diet with selenium compounds has been associated with both beneficial and deleterious effects on sperm function, depending on the chemical form of selenium. We conducted a randomized, controlled, and blinded intervention study on the effects of selenium in food on semen quality. Eleven healthy men were fed a controlled diet of foods naturally high or low in selenium for 120 days while confined in a metabolic research unit. Dietary selenium was 47 microg/d for the first 21 days, then either 13 microg/d or 297 microg/d for 99 days, resulting in significant changes in selenium concentrations in blood and semen. Seminal plasma selenium concentration increased 50% with high selenium and decreased 40% with low selenium. The fraction of motile sperm in the high-selenium group decreased by 32% by week 13 and ended 18% lower than baseline. Selenium concentrations changed in seminal plasma but not in sperm, and serum androgen concentrations were unchanged in both groups, indicating this effect was neither androgen dependent nor caused by a change in the selenium supply to the testes. Serum triiodothyronine decreased and thyroid-stimulating hormone increased in the high-selenium group, suggesting that altered thyroid hormone metabolism may have affected sperm motility. Although this decrease in sperm motility does not necessarily predict decreased fertility, the increasing frequency of selenium supplementation in the healthy population suggests the need for larger studies to more fully assess this potential side effect.
764
Journal of Andrology, Vol. 22, No. 5, September/October 2001
Copyright
American Society of Andrology
Effects of Dietary Selenium on Sperm Motility in
Healthy Men
WAYNE CHRIS HAWKES* AND PAUL J. TUREK†
From the
*
United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition
Research Center, University of California at Davis, Davis, California; and †Department of Urology, School of
Medicine, University of California, San Francisco, California.
ABSTRACT: A deficiency of dietary seleniumleads to immotile,de-
formed sperm and infertility in rats, whereas supplementation of the
diet with selenium compounds has been associated with both ben-
eficial and deleterious effects on sperm function, depending on the
chemical form of selenium. We conducted a randomized, controlled,
and blinded intervention study on the effects of selenium in food on
semen quality. Eleven healthy men were fed a controlled diet of
foods naturally high or low in selenium for 120 days while confined
in a metabolic research unit. Dietary selenium was 47 g/d for the
first 21 days, then either 13 g/d or 297 g/d for 99 days, resulting
in significant changes in selenium concentrations in blood and se-
men. Seminal plasma selenium concentration increased 50% with
high selenium and decreased 40% with low selenium. The fraction
of motile sperm in the high-selenium group decreased by 32% by
week 13 and ended 18% lower than baseline. Selenium concentra-
tions changed in seminal plasma but not in sperm, and serum an-
drogen concentrations were unchanged in both groups, indicating
this effect was neither androgen dependent nor caused by a change
in the selenium supply to the testes. Serum triiodothyronine de-
creased and thyroid-stimulating hormone increased in the high-se-
lenium group, suggesting that altered thyroid hormone metabolism
may have affected sperm motility. Although this decrease in sperm
motility does not necessarily predict decreased fertility, the increas-
ing frequency of selenium supplementation in the healthy population
suggests the need for larger studies to more fully assess this poten-
tial side effect.
Key words: Semen volume, hypothyroidism, nutrition, selenium
supplementation, cancer chemoprevention.
J Androl 2001;22:764–772
S
elenium is an essential trace nutrient for humans and
animals. Selenium deficiency has been linked to re-
productive problems in rats, mice, chickens, pigs, sheep,
and cattle (Combs and Combs, 1986), and supplementa-
tion with selenium has been reported to improve repro-
ductive performance in sheep and mice (Tang et al, 1991;
Van Ryssen et al, 1992). Selenium is required for normal
testicular development and spermatogenesis in rats (Beh-
ne et al, 1996), mice, and pigs (Combs and Combs, 1986).
Serum selenium is reported to be lower in men with oli-
gospermia and azoospermia than in controls (Krsnjavi et
al, 1992).
Selenium, in the form of selenocysteine, functions as
the catalytic center in the active sites of at least 9 human
enzymes, including 4 glutathione peroxidase antioxidant
enzymes (Mills, 1959; Cohen and Takahashi, 1986;
Zhang et al, 1989; Chu et al, 1996), 3 iodothyronine
This work was supported by the US Department of Agriculture through
the intramural research programs of the Agricultural Research Service.
Correspondence to: Dr Chris Hawkes, USDA Pomology, University of
California at Davis, One Shields Avenue, Davis, CA 95616-8685 (e-mail:
chawkes@whnrc.usda.gov).
Received for publication June 30, 2000; accepted for publication Feb-
ruary 28, 2001.
deiodinases involved in thyroid hormone metabolism
(Larsen and Berry, 1995; Salvatore et al, 1996), thiore-
doxin reductase involved in antioxidation and signal
transduction (Gladyshev et al, 1996), and selenophospha-
te synthetase in the selenoprotein synthesis pathway (Low
et al, 1995). Many other selenocysteine-containing pro-
teins have been reported in humans and animals, but their
functions have not been established (Wilhelmsen et al,
1981; Hawkes et al, 1985a,b; Behne et al, 1995).
The selenodeiodinase enzymes (types I, II, and III io-
dothyronine deiodinases) control the metabolism of thy-
roid hormone, which is essential for the normal devel-
opment (Defranca et al, 1995) and function (Latchou-
mycandane et al, 1997) of testes in rats. In humans, adult
hyperthyroidism has been associated with increased lu-
teinizing hormone (LH) and follicle-stimulating hormone
(FSH) responses to exogenous gonadotropin-releasing
hormone, gynecomastia, increased sex hormone-binding
globulin, and an increase in libido, whereas adult hypo-
thyroidism has been associated with testicular resistance
to gonadotropins, decreased testosterone and sex hormone
binding globulin, diminished libido, and impotence, but
direct effects of thyroid hormone on the testes have not
been reported in adults (Jannini et al, 1995).
Phospholipid hydroperoxide glutathione peroxidase is
765Hawkes and Turek · Dietary Selenium and Sperm Motility
expressed at higher levels in rat testes than in any other
tissue (Roveri et al, 1994) and is present in the head and
midpiece of sperm cells (Godeas et al, 1997), where it
protects the sperm from oxidative damage and serves a
dual role as the mitochondrial capsule selenoprotein (Ur-
sini et al, 1999), which is one of 3 proteins required for
maintenance of the crescent structure of sperm mitochon-
dria (Aho et al, 1996). Glutathione peroxidase activity has
also been reported in human seminal plasma (Saaranen et
al, 1989). Although it is difficult to deplete testes of se-
lenium because of the organ’s tenacious affinity for the
element, sperm from second- and third-generation sele-
nium-deficient rats are largely immotile and show a high
incidence of sperm midpiece defects due to disorganiza-
tion of the mitochondrial helix (Calvin et al, 1981).
We fed 11 men a controlled diet of conventional foods
with naturally high or low selenium contents for 120 days
while confined in a metabolic research unit to assess the
metabolic and physiological effects of dietary selenium.
In this report we present results describing the effects of
dietary selenium on the male reproductive system.
Materials and Methods
Subjects
Twelve healthy men were recruited from a pool of 148 volunteer
candidates who passed an initial telephone screening. Health of
candidates was assessed by medical history, physical examina-
tion, semen analysis, hematological and clinical chemistry tests,
psychological testing, resting electrocardiogram, hepatitis, syph-
ilis, tuberculosis, and human immunodeficiency virus antibody
tests. Tests for alcohol, tobacco, and drug use were also per-
formed. Candidates were excluded for weight for height greater
than 125% of ideal (Metropolitan Life Insurance Co, 1980); use
of selenium supplements or selenium-containing shampoos; ab-
normal blood cell counts, clinical chemistries, or semen analysis;
indications of substance abuse; habitual use of tobacco or alco-
hol; chronic use of medications; history of psychiatric illness;
and history of thyroid disease, hepatitis, heart disease, diabetes,
hypertension, or hyperlipidemia. The study protocol was ap-
proved by the Human Subjects Review Committees of the Uni-
versity of California at Davis and the US Department of Agri-
culture. The protocol was reviewed with the study volunteers
and their informed consent was obtained in writing prior to the
study, in accordance with the Common Federal Policy for Pro-
tection of Human Research Subjects. One subject withdrew from
the study after 60 days for personal reasons unrelated to the
study, and his data were not included. The 11 subjects who com-
pleted the study were aged 20 to 45 years, and had normal
weight (75.5
10.6 kg), height (178
5.5 cm), and body mass
index (23.4
3.4 kg/m
2
).
The subjects were confined in a metabolic research unit for
120 days under 24-hour supervision by staff members. Subjects
participated in two required 2-mile walks per day, and were al-
ways escorted by staff members when out of the metabolic re-
search unit and when meeting with visitors. Due to other inves-
tigations being conducted during this study, the subjects under-
went frequent blood draws and other minimally invasive pro-
cedures throughout the study.
Experimental Diets and Treatments
Subjects were fed a diet composed of conventional foods, based
on beef and rice as staples, plus a vitamin and mineral supple-
ment tablet, free of selenium (Unicap M; Upjohn Co, Kalama-
zoo, Mich). The total diet (Table 1) contained at least 100% of
the US recommended dietary allowance (RDA) for all nutrients
except magnesium (56%), calcium (72%), and selenium, and ap-
proximated the composition of a typical US diet (US Department
of Agriculture, 1991). All meals were consumed completely un-
der the direct observation of staff members.
For the first 21 days, all subjects were fed a diet that provided
47
g/d of selenium (RDA
55
g/d; [Panel on Dietary An-
tioxidants and Related Compounds, 2000]) at the average energy
intake of 11.7 MJ/d to adapt the subjects to the experimental
diet and to stabilize their body weights. For the remainder of the
study, the energy intake of each subject was adjusted as needed
to maintain body weight by increasing or decreasing all com-
ponents of the diet proportionally. The subjects were randomly
assigned to one of two groups after blocking into 6 pairs
matched for blood selenium concentrations. For the remaining
99 days of the study, one group was fed a diet that provided 13
g/d of selenium and the other group was fed a diet that pro-
vided 297
g/d, at the average energy intake of 11.7 MJ/d. The
selenium intake from the low-selenium diet was as low as could
be achieved with foods and was lower than the minimum intake
required to prevent Keshan disease, a viral cardiomyopathy as-
sociated with selenium deficiency in China (Yang et al, 1987),
and the only example of selenium deficiency disease known in
humans. The selenium intake from the high-selenium diet was
as high as achievable, given the selenium content of the South
Dakota beef used and the design goal that half the dietary se-
lenium be from animal sources and half from plant sources, yet
remained less than the maximum ‘‘oral reference dose’’ of 350
g selenium/day considered safe by the US Environmental Pro-
tection Agency (EPA; Poirier, 1994) and less than the tolerable
upper intake level of 400
g/d set by the Dietary Reference
Intake (DRI) Committee (Panel on Dietary Antioxidants and Re-
lated Compounds, 2000). On day 110 only (week 16), all sub-
jects were fed the low-selenium diet and were administered an
oral dose of Na
274
SeO
3
(10
g selenium for the low-selenium
group, or 300
g selenium for the high-selenium group) with
the morning meal as part of a metabolic tracer study. Extra blood
specimens were obtained the morning of day 110 before the
stable isotopes were administered to avoid any ‘‘pharmacologi-
cal’’ effects of the sodium selenite dose.
The only difference between the experimental diets was the
geographic origin of the rice and beef staples, which were ob-
tained from regions with either very high or very low soil se-
lenium; all other aspects of the 3 diets were identical. Composite
samples of each diet were analyzed for nutrient contents at a
commercial laboratory (Corning-Hazelton, Madison, Wis) using
standard methods (Association of Official Analytical Chemists,
1990). The selenium contents of the 3 diets were analyzed in-
766 Journal of Andrology · September/October 2001
Table 1. Diet composition*
Component Daily Intake (per 11.7 MJ) RDA†
Protein
Carbohydrate 68.5 g (10.6% of energy)
357 g (55.0% of energy) 63 g
NA
Fat
Saturated fat‡
Monounsaturated fat‡
Polyunsaturated fat‡
99.2 g (34.4% of energy)
32.0 g
35.7 g
25.8 g
NA
NA
NA
NA
Fiber*
Cholesterol*
Selenium (stabilization diet)
Selenium (low-selenium diet)
Selenium (high-selenium diet)
6.1 g
253 mg
47 g
13 g
297 g
NA
NA
55 g
55 g
55 g
Iodine†
Calcium
Iron
Magnesium
Phosphorus
Zinc
Copper
Manganese
Potassium
280 g
572 mg
28.3 mg
195 mg
1013 mg
28.4 mg
2.93 mg
3.68 mg
2645 mg
150 g
800 mg
10 mg
350 mg
800 mg
15 mg
1.5–3 mg§
2–5 mg§
1875–5625 mg§
* Unless otherwise indicated, values are from analyses of composites of foods from each experimental diet. Contributions from the daily vitaminand
mineral supplement are included. NA indicates not applicable.
† RDA indicates recommended dietary allowance (National Research Council Committee on Dietary Allowances, 1989).
‡ Dietary component estimated from food composition tables (US Department of Agriculture, 1991).
§ Estimated Safe and Adequate Daily Dietary Intake (National Research Council Committee on Dietary Allowances, 1980).
house as described below. There were no significant differences
detected between the 3 diets in their contents of protein, fat,
carbohydrate, energy, cysteine, methionine, iodine, mercury,
cadmium, calcium, copper, iron, magnesium, manganese, mo-
lybdenum, nickel, phosphorus, potassium, sodium, or zinc (data
not shown). Subjects and the analysts were blinded to which
subjects were eating which diets.
Laboratory Measurements
Blood samples were collected at 0700 hours, after an overnight
fast of 12 hours. Erythrocyte, serum, and plasma samples were
immediately frozen and stored at
70
C until analyzed. Serum
samples were refrigerated until analyzed each night at a refer-
ence laboratory (Chemzyme Plus, SmithKline-Beecham). Serum
hormones were measured by radioimmunoassay (Diagnostic
Products Corporation, Los Angeles, Calif). Selenium was mea-
sured by fluorescence-derivatization high-performance liquid
chromatography (Hawkes and Kutnink, 1996). Protein was de-
termined by an automated colorimetric method (Hawkes and
Craig, 1990).
Semen Collections
Semen samples were obtained by masturbation during weeks 3
(baseline), 8, 13, and 17. During each week of sampling, 3 spec-
imens were obtained, separated by 72 hours of abstinence each
time. Volume was measured in all 3 specimens and averaged to
give a mean volume for each week of sampling. The third spec-
imen of each set was subjected to standard semen analysis ac-
cording to World Health Organization (WHO) guidelines using
the WHO strict criteria (WHO, 1992). Sperm mean forward ve-
locity was measured by computer-assisted videomicroscopy
(Hobson Sperm Tracker; Biogenics, Napa, Calif) from video-
tapes prepared during the manual semen analysis of the third
specimen.
Sperm Preparation
Seminal plasma and washed sperm were prepared from the first
and second specimens of each set. Liquefied semen was centri-
fuged at 2000
gfor 10 minutes at room temperature to remove
sperm and the seminal plasma was aspirated and saved. Cloudy
samples of seminal plasma were clarified by centrifugation at
12000
gfor 10 minutes and the pellets were discarded. The
sperm pellet was washed once with normal saline and repelleted
at 2000
gfor 10 minutes at room temperature. Washed sperm
were resuspended in one-half the original semen volume of 50
mM Tris-HCl, 0.5% Triton X-100 pH 7.8. Sperm and seminal
plasma samples were stored at
70
C until analyzed. The sele-
nium concentrations of the first and second specimens obtained
each week were averaged.
Statistical Analysis
The data were analyzed by two-way repeated measures analysis
of variance, using each subject’s baseline measurement as a cov-
ariate to control for the initial differences between subjects. The
analyses were performed with BMDP 7.0 program 2V, Analysis
of Variance and Covariance with Repeated Measures (SPSS,
Chicago, Ill), using a complete model: selenium, time, covariate,
and selenium
time interaction. Significant differences between
groups at each time point were tested with the Student-Newman-
Keuls procedure. A probability of .05 or less was considered
significant.
767Hawkes and Turek · Dietary Selenium and Sperm Motility
Figure 1. Changes in blood plasma selenium concentrations. Points rep-
resent the averages of the within-subject changes from baseline for sub-
jects consuming the high-selenium diet () or the low-selenium diet ().
Asterisks designate the time points at which the group means were sig-
nificantly different.
Table 2. Effects of low-selenium and high-selenium diets on selenium and serum hormone status
Parameter
Low-selenium Diet
Baseline value†
(Mean SD) Ending Value‡
(Mean SD)
High-selenium Diet
Baseline Value
(Mean SD) Ending Value
(Mean SD)
Statistical Analysis*
Se, PTime, PSe Time,
P
Blood plasma selenium, mg/L
Erythrocyte selenium, mg/L
Seminal plasma selenium, g/L
Sperm selenium, ng/mg protein
3,3,5-triiodothyronine (T
3
), nmol/L
Thyroid-stimulating hormone, mU/L
Total testosterone, ng/dL
Free testosterone, pg/mL
Follicle-stimulating hormone, U/mL
Luteinizing hormone, U/mL
Prolactin, ng/mL
Estradiol, pg/mL
Progesterone, ng/mL
0.13 0.02
0.160 0.009
52 17
4.5 1.7
1.57 0.25
1.69 0.30
676 193
33 5.5
3.3 3.0
1.6 0.6
17 4.4
26 9.4
0.99 0.22
0.08 0.02
0.116 0.011
33 11
5.1 2.6
1.64 0.16
1.77 0.46
633 197
29 4.7
3.4 3.0
2.4 0.6
16 3.4
29 17
0.93 0.23
0.12 0.02
0.168 0.024
43 11
4.3 2.2
1.82 0.36
2.25 0.81
576 194
26 6.9
2.7 1.4
2.0 1.0
12 6.8
19 8.2
0.93 0.36
0.25 0.04
0.278 0.021
63 15
3.4 0.9
1.57 0.07
2.96 1.05
669 257
31 12
2.7 1.4
2.3 0.9
16 9.7
25 17
0.84 0.16
.0001
...
.004
...
.013
...
...
...
...
...
...
...
...
.0006
.05
...
...
...
.011
...
.020
...
...
...
...
...
.012
.01
...
...
.048
.031
...
...
...
...
...
...
...
* Analysis of variance and covariance with repeated measures, baseline values as covariates, BMDP Program 2V. Se indicates grand means different between groups; time, ending different
from baseline; and Se time interaction, groups diverge over time.
† Single measurements in blood on day 22 or average selenium in the first and second semen specimens obtained during week 3.
‡ Single measurements in blood on day 110 or average selenium in the first and second semen specimens obtained during week 17.
Results
Selenium Status
Ninety-nine days consuming the low-selenium and high-seleni-
um diets was sufficient to significantly change selenium status
in blood and seminal plasma. Selenium concentrations in blood
plasma (Figure 1) began to change within 3 days of changing
the diet and continued to change throughout the study. By the
end of the study, blood plasma selenium concentrations had in-
creased by 70% in the high-selenium group and decreased by
40% in the low-selenium group (Table 2). The pattern of changes
in seminal plasma selenium concentration (Figure 2) was similar
to the pattern observed in blood plasma, increasing by 50% in
the high-selenium group and decreasing by 40% in the low-
selenium group by the end of the study (Table 2). Seminal plas-
ma selenium concentration reached a plateau by week 8, and did
not change significantly thereafter. At the end of the study, sem-
inal plasma selenium concentrations were about 20% of, and
were correlated with, blood plasma selenium concentrations (r
.68, P
.01). However, the changes in selenium status were
not uniform throughout the body. Erythrocyte selenium concen-
tration increased by 65% in the high-selenium group and de-
creased by 37% in the low-selenium group. On the other hand,
selenium concentrations in sperm, whether expressed as simple
concentrations, as specific concentrations per mg of protein
(shown in Table 2), or as total selenium per ejaculate, did not
change significantly in either group, nor were there any signifi-
cant differences in sperm selenium between groups.
Semen Quality
The fraction of motile sperm decreased by an average of
32% in the high-selenium subjects at week 13 (Figure 3),
but ended only 17% lower than the baseline value at week
17 (Table 3). Sperm motility increased by an average of
10% in the low-selenium group at week 13, but was no
longer significantly different from baseline by
768 Journal of Andrology · September/October 2001
Figure 2. Changes in seminal plasma selenium concentrations. Points
represent the averages of the within-subject changes from baseline for
subjects consuming the high-selenium diet () or the low-selenium diet
(). Asterisks designate the time points at which the group means were
significantly different.
Table 3. Effects of low-selenium and high-selenium diets on semen quality
Parameter
Low-selenium Diet
Baseline Value†
(Mean SD) Ending Value‡
(Mean SD)
High-selenium Diet
Baseline Value
(Mean SD) Ending Value
(Mean SD)
Statistical Analysis*
Se, PTime, PSe Time,
P
Sperm concentration, million/mL
Semen volume, mL§
Sperm total number, millions
Motile sperm, fraction
Progressive sperm, %
Mean forward velocity, m/s
Oval morphology, %
Tapered morphology, %
Amorphous morphology, %
Tail defects, %
Headless sperm, %
Tailless sperm, %
153 123
3.6 2.7
406 307
0.542 0.086
90.3 8.3
51.2 5.6
4.7 1.0
42.2 16.0
34.5 13.6
1.8 2.6
5.7 4.9
1.0 0.9
77 39
3.3 1.8
276 260
0.532 0.196
74.7 18.8
40.6 10.8
13.0 12.7
39.0 18.0
35.5 19.6
0.3 0.8
3.0 3.9
3.8 3.9
119 46
3.4 1.8
472 376
0.588 0.161
81.6 16.0
46.7 10.0
6.0 2.0
48.0 8.7
28.8 9.5
3.0 2.5
5.4 3.0
0.8 1.3
52 21
3.0 1.2
109 15
0.488 0.193
78.8 15.1
42.0 8.8
6.2 4.8
49.2 13.9
28.6 9.7
1.6 2.2
1.2 1.8
9.0 9.2
...
...
...
.031
...
...
...
...
...
...
...
...
.045
...
.021
...
...
.026
...
...
...
...
.028
.021
...
...
...
.010
...
...
...
...
...
...
...
...
* Analysis of variance and covariance with repeated measures, baseline values as covariates, BMDP Program 2V. Se indicates grand means different between groups; time, ending different
from baseline; and Se time interaction, groups diverge over time.
† Value from semen analysis of third semen specimen obtained during week 3.
‡ Value from semen analysis of third semen specimen obtained during week 17.
§ Average of semen volumes of all three specimens during week 3 or week 17.
Figure 3. Changes in the fraction of motile sperm. Points represent the
averages of the within-subject changes from baseline for subjects con-
suming the high-selenium diet () or the low-selenium diet ().Asterisks
designate the time points at which the group means were significantly
different.
week 17. The maximum effect of dietary selenium was
observed at week 13, when the fraction of motile sperm
in the low-selenium group was 50% greater than in the
high-selenium group. There was a large and highly sig-
nificant decrease in the concentration and total number of
sperm in both groups during the study (Table 3). The
average sperm concentration of the 11 subjects decreased
gradually from 137 million/mL to 65.6 million/mL, and
the average number of sperm per ejaculate decreased from
436 million to 200 million, with no significant differences
between groups. Mean forward velocity decreased by an
average of 16% in the 11 subjects (Table 3), but was not
significantly different between groups. Similarly, the
abundance of headless forms of sperm decreased by al-
769Hawkes and Turek · Dietary Selenium and Sperm Motility
Figure 4. Changes in serum T
3
concentrations. Points represent the av-
erages of the within-subject changes from baseline for subjects consum-
ing the high-selenium diet () or the low-selenium diet (). Asterisks
designate the time points at which the group means were significantly
different.
most two-thirds in both groups, whereas the abundance
of tailless forms increased, again with no significant dif-
ferences between groups.
Serum Hormones
By week 8, serum 3,3
,5-triiodothyronine (T
3
) had in-
creased an average of 14% in the low-selenium subjects
and decreased an average of 23% in the high-selenium
subjects (Figure 4), and remained significantly different
between groups throughout the study. Serum T
3
ended 8%
higher on average in the low-selenium subjects and 11%
lower on average in the high-selenium subjects. Serum
thyrotropin increased significantly by 32% over its base-
line concentration in the high-selenium group but did not
change significantly in the low-selenium group (Table 2).
There were no significant changes in the serum levels,
nor any significant differences between groups in free or
total testosterone, FSH, LH, prolactin, progesterone, or
estradiol.
Discussion
This appears to be the first report of dietary selenium
directly affecting sperm motility in humans. However,
there are several reports in the literature associating high
seminal plasma selenium with impaired sperm motility in
humans (Bleau et al, 1984; Takasaki et al, 1987; Hansen
and Deguchi, 1996). Supplementation of rat diets with
levels of selenium approximately 4 times higher than was
used in the present study has also been reported to cause
a decrease in sperm motility (Kaur and Parshad, 1994).
Severely selenium-deficient rats have lowered serum
testosterone concentrations (Behne et al, 1996). However,
we did not observe any significant changes in serum an-
drogens in either group, perhaps because of the much
smaller changes in selenium status in our study. The lack
of serum androgen changes in the present study indicates
the effect of dietary selenium on sperm motility was in-
dependent of the pituitary-testes hormonal axis. Our ob-
servation that sperm selenium concentrations were un-
changed shows that dietary selenium’s effect was also not
due to increased selenium in sperm, and implies that testis
selenium was also unchanged. This is consistent with ob-
servations from rat studies in which the selenium content
of testes was unchanged by dietary selenium deficiency
or excess (Behne et al, 1988). A change in spermatogen-
esis therefore seems an unlikely explanation for this effect
of selenium on motility, as neither serum androgens nor
testis selenium metabolism were perturbed.
Although seminal plasma selenium increased by almost
half, there is no known mechanism to explain how high
selenium concentrations in seminal plasma could decrease
sperm motility. Selenium toxicity seems unlikely as the
intake of 297
g/d used in this study was less than the
oral reference dose of 350
g/d considered safe for life-
time consumption by EPA (Poirier, 1994) and was well
under the tolerable upper intake level of 400
g/d set by
the DRI Committee (Panel on Dietary Antioxidants and
Related Compounds, 2000). It is possible that the admin-
istration of pure sodium selenite on day 110 for the tracer
study could have affected sperm motility measured during
week 17 (days 111–117). However, the changes in sperm
motility were already significant at week 13, before the
stable isotopes were administered, and the apparent mo-
tility changes between week 13 and week 17 were not
statistically significant in either group.
Because seminal plasma selenium originates from ep-
ithelial secretions of the accessory sex glands (prostate
gland, seminal vesicles, and epididymis), the changes in
seminal plasma selenium indicate that the selenium sup-
ply to these glands changed with dietary selenium. Be-
cause sperm selenium (and by inference testis selenium)
and serum androgens did not change, the effect of sele-
nium on motility was most likely mediated by secretions
from the accessory sex glands, either during sperm mat-
uration or at ejaculation. Although there is little evidence
to support a direct toxic effect of selenium in seminal
plasma on sperm motility, there are many examples of
factors present in seminal plasma that modulate sperm
motility: fructose, which supplies fuel for respiration; an-
giotensin II (O’Mahony et al, 2000); calcium (Kilic et al,
1996); relaxin (Lessing et al, 1986); and epididymal mo-
tility inhibitor proteins (Turner and Giles, 1982; Turner
and Reich, 1987), to name a few. More work onthe forms
and functions of selenium in semen and the accessory sex
glands is required to understand how an increased supply
of selenium might lead to decreased sperm motility.
770 Journal of Andrology · September/October 2001
Serum T
3
levels decreased within 23 days of starting
the high-selenium diet, with a corresponding increase in
serum thyrotropin, suggesting establishment of a subclin-
ical hypothyroid state in that group. Although the de-
crease in circulating T
3
concentrations was quite modest,
the positive response of thyrotropin in the high selenium
group confirms the presence of a physiologically hypo-
thyroid state. It is tempting to speculate that the decreased
sperm motility observed in this study may have been re-
lated to this subclinical hypothyroid state. The pattern of
changes in sperm motility (Figure 3) and T
3
(Figure 4)
are similar, with the maximum change in T
3
at week 8
preceding the maximum change in motility at week 13.
The literature on thyroid hormone and sperm function
is consistent with a role of thyroid hormone in the reduc-
tion of sperm motility by dietary selenium. Men with hy-
pothyroidism have been reported to have lower sperm
motility than euthyroid controls (Corrales-Hernandez et
al, 1990) and thyroxine replacement in men with hypo-
thyroidism is reported to improve sperm motility (Kumar
et al, 1990). There is ample evidence that thyroid hor-
mone is essential to the normal development of the testes
in the neonate (Cooke et al, 1994; Defranca et al, 1995;
Palmero et al, 1995; Hardy et al, 1996), and there is at
least one report that thyroid hormone acts on the neonatal
testes by regulating the expression of estrogen and andro-
gen receptors in Sertoli cells (Panno et al, 1996). There
are also reports of proteins in mouse kidney (Meseguer
and Catterall, 1990; Sole et al, 1996) and rat liver (Dill-
mann et al, 1977) whose expression is regulated by both
thyroid hormone and androgens. Because the accessory
sex glands are developmentally related to the kidneys it
is reasonable to speculate that thyroid hormone may also
modulate the androgen responses of these organs as well.
Such a mechanism would help explain how sperm motil-
ity was decreased without any significant changes in the
levels of testosterone or other reproductive hormones. Al-
though our observations are consistent with involvement
of thyroid hormone, other mechanisms cannot be exclud-
ed.
In addition to the effects of dietary selenium on sperm
motility, we also observed an overall decrease in sperm
production in both groups, with sperm concentration and
total sperm decreasing by more than 50% during the
study. We could not identify any aspect of the diet, nor
any change in the health status of the subjects that could
account for such a large decrease; in fact, the overall
health of the subjects seemed to improve during the study,
as is typical in our metabolic studies. The decreased
sperm production was not associated with a change in free
or total testosterone, or any other reproductive hormone
measured. Because the baseline semen specimens were
obtained during the first week of May and the final spec-
imens were taken during the first week of August, a plau-
sible explanation for the decreased sperm counts might
be the seasonal variation in human sperm production,
which can be as great as 50% and is reported to peak in
late winter or spring and to be at a minimum in late sum-
mer (Tjoa et al, 1982; Spira, 1984; Spira and Ducot, 1985;
Levine et al, 1988; Reinberg et al, 1988; Politoff et al,
1989; Saint Pol et al, 1989; Sood et al, 1993). It may also
be relevant that record high temperatures occurred in San
Francisco during 1993 on July 31, August 1, and August
2, the week immediately preceding the final set of semen
collections, as there have been some reports that the an-
nual variation of human sperm counts is related to vari-
ations of air temperature (Sood et al, 1993; Lerchl and
Nieschlag, 1997).
Our observation that a high-selenium diet led to de-
creased sperm motility points to the possibility that high
selenium intakes might be associated with impaired male
fertility. Because of the small number of subjects in this
study, the results must be interpreted with caution. Rep-
lication of these observations in larger numbers of sub-
jects is required to lend confidence to our interpretations.
Because recent reports of selenium’s cancer protective ef-
fects in humans (Clark et al, 1996) may lead to increased
usage of high-dose selenium supplements, it is important
to establish if the observations we made in the metabolic
research unit are relevant to free-living men consuming
selenium supplements. Because we did not observe any
change in selenium content of sperm in 14 weeks, future
studies should include several complete cycles of sper-
matogenesis to ensure the complete effects of dietary se-
lenium on semen quality are observed.
Acknowledgments
The authors gratefully acknowledge the excellent laboratory assistance of
Mark Kutnink, Denise Gretz, and Manuel Tengonciang at the Western
Human Nutrition Research Center, and Raymond Tom at the University
of California at San Francisco. We thank the recruiting, metabolic kitchen,
nursing, and administrative staff of Bionetics Corporation and the Bioan-
alytical Support Laboratory staff of Western Human Nutrition Research
Center for their assistance with the conduct of this study. We are also
indebted to Dr Virginia Gildengorin and Dr Mei-Miao Wu for advice and
assistance with the statistical analyses. We are especially thankful to Dr
Yiming Xia of the Chinese Academy of Preventive Medicine for her
assistance obtaining high- and low-selenium rice from China. Mention of
a trade name, proprietary product, or specific equipment does not con-
stitute a guarantee or warranty by the US Department of Agriculture, nor
does it imply approval to the exclusion of other products that may be
suitable. The opinions expressed herein represent those of the authorsand
do not necessarily represent those of the US Department of Agriculture.
References
Aho H, Schwemmer M, Tessmann D, Murphy D, Mattei G, Engel W,
Adham IM. Isolation, expression, and chromosomal localization of
771Hawkes and Turek · Dietary Selenium and Sperm Motility
the human mitochondrial capsule selenoprotein gene (MCSP). Gen-
omics. 1996;32:184–190.
Association of Official Analytical Chemists. Official Methods of Analysis.
15th ed. Arlington, Va: AOAC; 1990.
Behne D, Hilmert H, Scheid S, Gessner H, Elger W. Evidence forspecific
selenium target tissues and new biologically important selenoproteins.
Biochim Biophys Acta. 1988;966:12–21.
Behne D, Weiler H, Kyriakopoulos A. Effects of selenium deficiency on
testicular morphology and function in rats. J Reprod Fertil. 1996;106:
291–297.
Behne D, Weissnowak C, Kalcklosch M, Westphal C, Gessner H, Kyr-
iakopoulos A. Studies on the distribution and characteristics of new
mammalian selenium-containing proteins. Analyst. 1995;120:823–
825.
Bleau G, Lemarbre J, Faucher G, Roberts KD, Chapdelaine A. Semen
selenium and human fertility. Fertil Steril. 1984;42:890–894.
Calvin HI, Wallace E, Cooper GW. The role of selenium in the organi-
zation of the mitochondrial helix in rodent spermatozoa. In: Spallholz
JE, Martin JL, Ganther HE, eds. Selenium in Biology and Medicine.
Westport, Conn: Avi Publishing; 1981:319–324.
Chu FF, DeSilva HAR, Esworthy RS, Boteva KK, Walters CE, Roses A,
Rao PN, Pettenati MJ. Polymorphism and chromosomal localization
of the GI-form of human glutathione peroxidase (GPX2) on 14q24.1
by in situ hybridization. Genomics. 1996;32:272–276.
Clark LC, Combs GF Jr, Turnbull BW, et al. Effects of selenium supple-
mentation for cancer prevention in patients with carcinoma of the
skin. A randomized controlled trial. JAMA. 1996;276:1957–1963.
Cohen HJ, Takahashi K. Human plasma glutathione peroxidase isolation
and characterization of a unique selenium enzyme. In: Proceedings
of the 78th Annual National Meeting of the American Society For
Clinical Investigation. Washington, DC: ASCI; May 1986:34.
Combs GF Jr, Combs SB. The Role of Selenium in Nutrition. San Diego:
Academic Press; 1986.
Cooke PS, Zhao YD, Bunick D. Triiodothyronine inhibits proliferation
and stimulates differentiation of cultured neonatal Sertoli cells: pos-
sible mechanism for increased adult testis weight and sperm produc-
tion induced by neonatal goitrogen treatment. Biol Reprod. 1994;51:
1000–1005.
Corrales-Hernandez JJ, Miralles-Garcia JM, Garcia-Diez LC. Primary hy-
pothyroidism and human spermatogenesis. Arch Androl. 1990;25:21–
27.
Defranca LR, Hess RA, Cooke PS, Russell LD. Neonatal hypothyroidism
causes delayed Sertoli cell maturation in rats treated with propylthio-
uracil: evidence that the Sertoli cell controls testis growth. Anat Rec.
1995;242:57–69.
Dillmann WH, Silva E, Surks MI, Oppenheimer JH. Studies of a thyroid
hormone and androgen dependent protein in rat liver cytosol. Acta
Endocrinol (Copenhagen). 1977;84:548–558.
Gladyshev VN, Jeang KT, Stadtman TC. Selenocysteine, identified as the
penultimate C-terminal residue in human T-cell thioredoxinreductase,
corresponds to TGA in the human placental gene. Proc Natl Acad Sci
USA. 1996;93:6146–6151.
Godeas C, Tramer F, Micali F, Soranzo M, Sandri G, Panfili E. Distri-
bution and possible novel role of phospholipid hydroperoxide gluta-
thione peroxidase in rat epididymal spermatozoa. Biol Reprod. 1997;
57:1502–1508.
Hansen JC, Deguchi Y. Selenium and fertility in animals and man–a
review. Acta Vet Scand. 1996;37:19–30.
Hardy MP, Sharma RS, Arambepola NK, Sottas CM, Russell LD, Bunick
D, Hess RA, Cooke PS. Increased proliferation of Leydig cells in-
duced by neonatal hypothyroidism in the rat. J Androl. 1996;17:231–
238.
Hawkes WC, Craig KA. Adaptation of the bicinchoninic acid protein
assay to a continuous-flow autoanalyzer. Lab Robotics Automation.
1990;3:13–17.
Hawkes WC, Kutnink MA. High-performance liquid chromatographic-
fluorescence determination of traces of selenium in biological mate-
rials. Anal Biochem. 1996;241:206–211.
Hawkes WC, Wilhelmsen EC, Tappel AL. Abundance and tissue distri-
bution of selenocysteine-containing proteins in the rat. J Inorganic
Biochem. 1985a;23:77–92.
Hawkes WC, Wilhelmsen EC, Tappel AL. Subcellular distribution of se-
lenium-containing proteins in the rat. J Inorganic Biochem. 1985b;
25:77–93.
Jannini EA, Ulisse S, D’Armiento M. Thyroid hormone and male gonadal
function. Endocr Rev. 1995;16:443–459.
Kaur R, Parshad VR. Effects of dietary selenium on differentiation, mor-
phology and functions of spermatozoa of the house rat, Rattus rattus
L. Mutation Res. 1994;309:29–35.
Kilic S, Sarica K, Yaman O, Soygur T, Gogus O, Yaman LS. Effect of
total and ionized calcium levels of seminal fluid on sperm motility.
Urol Int. 1996;56:215–218.
Krsnjavi H, Grgurevic BA, Beker D, Romic Z, Krsnjavi A. Selenium and
fertility in men. Trace Elements Med. 1992;9:107–108.
Kumar BJ, Khurana ML, Ammini AC, Karmarkar MG, Ahuja MMS.
Reproductive endocrine functions in men with primary hypothyroid-
ism: effect of thyroxine replacement. Horm Res. 1990;34:215–218.
Larsen PR, Berry MJ. Nutritional and hormonal regulation of thyroid
hormone deiodinases. Ann Rev Nutr. 1995;15:323–352.
Latchoumycandane C, Gupta SK, Mathur PP. Inhibitory effects of hy-
pothyroidism on the testicular functions of postnatal rats. Biomed Lett.
1997;56:171–177.
Lerchl A, Nieschlag E. Impact of environmental temperature on human
scrotal temperatures. Biometeorology. 1997;14:215–221.
Lessing JB, Brenner SH, Colon JM, et al. Effect of relaxin on human
spermatozoa. J Reprod Med. 1986;31:304–309.
Levine RJ, Bordson BL, Mathew RM, Brown MH, Stanley JM, Star TB.
Deterioration of semen quality during summer in New Orleans. Fertil
Steril. 1988;49:900–907.
Low SC, Harney JW, Berry MJ. Cloning and functional characterization
of human selenophosphate synthetase, an essential component of se-
lenoprotein synthesis. J Biol Chem. 1995;270:21659–21664.
Meseguer A, Catterall JF. Cell-specific expression of kidney androgen-
regulated protein messenger RNA is under multihormonal control.
Mol Endocrinol. 1990;4:1240–1248.
Metropolitan Life Insurance Co. New Height and Weight Tables. 1979
Build Study. Chicago, Ill: Society of Actuaries and Association of
Life Insurance Medical Directors of America; 1980.
Mills GC. The purification and properties of glutathione peroxidase of
erythrocytes. J Biol Chem. 1959;234:502–506.
National Research Council. Committee on Dietary Allowances. Recom-
mended Dietary Allowances. 9th ed. Washington, DC: National Acad-
emy Press; 1980.
National Research Council. Committee on Dietary Allowances. Recom-
mended Dietary Allowances. 10th ed. Washington, DC: National
Academy Press; 1989.
O’Mahony OA, Djahanbahkch O, Mahmood T, Puddefoot JR, Vinson GP.
Angiotensin II in human seminal fluid. Hum Reprod. 2000;15:1345–
1349.
Palmero S, Prati M, Bolla F, Fugassa E. Tri-iodothyronine directlyaffects
rat Sertoli cell proliferation and differentiation. J Endocrinol. 1995;
145:355–362.
Panel on Dietary Antioxidants and Related Compounds. SoURLoN, Sub-
committee on Interpretation and Uses of DRIs, Standing Committee
on the Scientific Evaluation of Dietary Reference Intakes, Food and
Nutrition Board. Dietary Reference Intakes for Vitamin C, Vitamin E,
772 Journal of Andrology · September/October 2001
Selenium, and Carotenoids. Washington, DC: National Academy
Press; 2000.
Panno ML, Sisci D, Salerno M, et al. Thyroid hormone modulates an-
drogen and oestrogen receptor content in the Sertoli cells of peripub-
ertal rats. J Endocrinol. 1996;148:43–50.
Poirier KA. Summary of the derivation of the reference dose for seleni-
um. In: Mertz W, Abernathy CO, Olin SS, eds. Risk Assessment of
Essential Elements. Washington, DC: ILSI Press; 1994: 157–166.
Politoff L, Birkhauser M, Almendral A, Zorn A. New data confirming a
circannual rhythm in spermatogenesis. Fertil Steril. 1989;52:486–489.
Reinberg A, Smolensky MH, Hallek M, Smith KD, Steinberger E. Annual
variation in semen characteristics and plasma hormone levels in men
undergoing vasectomy. Fertil Steril. 1988;49:309–315.
Roveri A, Maiorino M, Nisii C, Ursini F. Purification and characterization
of phospholipid hydroperoxide glutathione peroxidase from rat testis
mitochondrial membranes. Biochim Biophys Acta. 1994;1208:211–
221.
Saaranen M, Suistomaa U, Vanha PT. Semen selenium content and sperm
mitochondrial volume in human and some animal species. Hum Re-
prod. 1989;4:304–308.
Saint Pol P, Beuscart R, Leroy-Martin B, Hermand E, Jablonski W. Circ-
annual rhythms of sperm parameters of fertile men. Fertil Steril. 1989;
51:1030–1033.
Salvatore D, Bartha T, Harney JW, Larsen PR. Molecular biological and
biochemical characterization of the human type 2 selenodeiodinase.
Endocrinology. 1996;137:3308–3315.
Sole E, Calvo R, Obregon MJ, Meseguer A. Effects of thyroid hormone
on the androgenic expression of KAP gene in mouse kidney. Mol Cell
Endocrinol. 1996;119:147–159.
Sood S, Reghunandanan R, Singh U, Reghunandanan V, Singh PI. Circ-
annual variation of sperm count and motility in men. Indian J Med
Sci. 1993;47:197–200.
Spira A. Seasonal variations of sperm characteristics. Arch Androl. 1984;
12(suppl):23–28.
Spira A, Ducot B. Physiologic changes in semen examination [in French].
Ann Biol Clin (Paris). 1985;43:55–61.
Takasaki N, Tonami H, Simizu A, et al. Semen selenium in male infer-
tility. Bull Osaka Med Sch. 1987;33:87–96.
Tang CC, Chen HN, Rui HF. The effects of selenium on gestation, fer-
tility, and offspring in mice. Biol Trace Elem Res. 1991;30:227–231.
Tjoa WS, Smolensky MH, Hsi BP, Steinberger E, Smith KD. Circannual
rhythm in human sperm count revealed by serially independent sam-
pling. Fertil Steril. 1982;38:454–459.
Turner TT, Giles RD. Sperm motility-inhibiting factor in rat epididymis.
Am J Physiol. 1982;242:R199–R203.
Turner TT, Reich GW. Influence of proteins in rat cauda epididymidal
lumen fluid on cauda sperm motility. Gamete Res. 1987;18:267–278.
US Department of Agriculture. Composition of Foods (Handbook 8). 10th
ed. Washington, DC: Government Printing Office; 1991.
Ursini F, Heim S, Kiess M, Maiorino M, Roveri A, Wissing J, Flohe L.
Dual function of the selenoprotein PHGPx during sperm maturation.
Science. 1999;285:1393–1396.
Van Ryssen JBJ, Bradfield GD, Van Malsen S, De Villers JF. Response
to selenium supplementation of sheep grazing cultivated pastures in
the natal midlands. J S Afr Vet Assoc. 1992;63:148–155.
Wilhelmsen EC, Hawkes WC, Motsenbocker MA, Tappel AL. Seleno-
cysteine-containing proteins other than glutathione peroxidase from
rat tissue. In: Spallholz JE, Martin JL, Ganther HE, eds. Selenium in
Biology and Medicine. Westport, Conn: Avi Publishing; 1981:535–
539.
World Health Organization. WHO Laboratory Manual for the Examina-
tion of Human Semen and Sperm Cervical Mucus Interaction. Cam-
bridge, United Kingdom: Cambridge University Press; 1992.
Yang GQ, Qian PC, Zhu LZ, Huang JH, Liu SJ, Lu MD, Gu LZ. Human
selenium requirements in China. In: Combs GF Jr, Levander OA,
Spallholz JE, Oldfield JE, eds. Selenium in Biology and Medicine.
New York, NY: Van Nostrand Reinhold; 1987: 589–607.
Zhang L, Maiorino M, Roveri A, Ursini F. Phospholipid hydroperoxide
glutathione peroxidase specific activity in tissues of rats of different
age and comparison with other glutathione peroxidases. Biochim Bio-
phys Acta. 1989;1006:140–143.
... Similarly, the same author in another study underlined the significance of the interracial variability, which leads to different proclivity among human races for isolated nutraceutical deficiencies (i.e., zinc, or selenium) [68]. Likewise, overdosing of selenium may alter the sperm selenoproiten(s) of the outer mitochondrial membrane and alter the thyroid hormone metabolism, both conditions associated with asthenospermia [69,70]. The irrational use of beta-carotene, a precursor (inactive form) to vitamin A, may also cause a side effect to sperm physiology. ...
... Reviews 43 [1][2][3][4][5][6][7][8]13,15,17,19,[21][22][23][25][26][27][28][29][30][31][32][33][35][36][37][38][39][40][41][42][43][44][46][47][48][49]68,84,[86][87][88] Original Research 33 [9][10][11][12]14,18,20,24,34,45,[50][51][52][53][54][55][56][57][58][59][60][61][63][64][65][66][67][69][70][71][72]79,85] Systematic Review 7 [62,73,75,77,78,81,82] Systematic Review and Meta-analyses 4 [74,76,80,83] Letter to the editor 1 [16] Table A1. Cont. ...
... Hand-searched/Reference list checked 29 [9,10,27,28,31,34,42,47,[49][50][51][52][53][54][55][58][59][60][61][63][64][65][66][67]69,70,81,82,87] ...
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... In another study selenium was found to decrease sperm motility in healthy men by altering thyroid hormone metabolism. However, this study only included 11 patients who were given up to 297 lg/day of selenium, which is an extremely high dose [29]. ...
Article
Background Male infertility has been related to an increased sperm DNA fragmentation index (DFI). Nutritional factors may improve sperm nuclear DNA integrity and thus pregnancy rates. Objective: To evaluate the effect of micronutrient supplementation on sperm DNA integrity in subfertile men and subsequent pregnancy rates. Methods In this retrospective comparative study 339 subfertile males were included on whom a sperm chromatin dispersion test (SCD) was performed as a method to detect DNA fragmentation, as well as an initial semen analysis. Of all, n = 162 received a nutritional management program for three months, consisting of two daily capsules of a standardized combined micronutrient formulation together with a guidance to diet modification and to lifestyle changes (study group). Each capsule contained L-carnitine, L-arginine, coenzyme Q10, zinc, vitamin E, folic acid, glutathione, and selenium. The control group consisted of those patients who did not receive the active treatment (n = 177), yet were instructed to engage in a healthy lifestyle, including a modification of their regular diet. The SCD test was repeated for both groups after three months. As part of the routine follow up, pregnancy rate was assessed six months after the second SCD test. Males with complete follow up and healthy female partners (aged 18 to 40 years) where included. Results Data of men with an initial mean DFI of >15% were analyzed first (n = 81;46 study and 35 control patients). After three months, both groups displayed a significant decrease of mean DFI values; however, the mean percent difference was higher in the study group (10.46 ± 1.20 % vs. 5.29 ± 0.57 %; p < .001). Then, the entire population was considered (n = 339). After three months, only the study group displayed a significant decrease of mean DFI initial values (10.48 ± 7.76 % to 6.51 ± 4.61%; p < .001); and the percent difference was higher in the study group (3.97 ± 0.28 % vs. 0.91 ± 0.28 %; p < .001). At six months follow-up, pregnancy rate was higher in the study group (27.78% vs. 15.25%, p = .002). Conclusion Both regimes significantly reduced sperm DNA fragmentation among subfertile men with a DFI >15%; however, when any baseline DFI value was considered, only micronutrient supplementation achieved a better result on DFI and thus pregnancy rate was higher.
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Selenium is a metalloid and an essential micronutrient needed by animals and humans at low concentrations but extremely toxic at high concentrations. It is found in the natural environment and can be present in soil, food, air, plant, and water. The chemistry of Se is linked to its different chemical forms. Se mobility and toxicity are strongly dependent on its redox state; from highly soluble oxyanions like selenate, selenite, and hydroselenite to elemental Se. However, selenate and selenite are the two predominant Se species in the water system because of their high solubility and low adsorption by sediments and soil. This provides most techniques the platform to focus on the removal of both selenite and selenate among other Se species. This chapter is focused on the occurrence and effective management of Selenate and Selenite in water.
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Water security and sanitation are precursors for socio-economic development, survival of flora and fauna, food security and healthy ecosystems. However, when these are compromised, they tend to have an adverse effect on the health of the populace and the socio-economic development of the entire society. This chapter investigates global laws and economic policies aimed at the abatement of toxic oxyanions (e.g. nitrate, fluoride, perchlorate etc) in aqua systems. Using a non-doctrinal cum systematic analysis, the extent of legal and economic instruments in controlling, reducing and preventing toxic oxyanion pollutants in water was examined. Relevant international treaties and instruments were analysed including the Universal Declaration on Human Rights (UDHR) 1948, the International Covenant on Economic, Social and Cultural Rights (ICESCR) 1966, the United Nations Convention on the Laws of the Sea (UNCLOS) 1982 and the United Nations Convention on the Law of the Non-Navigational Uses of International Watercourses (UNWC) 1997. Moreover, the use of different command and control (CAC) and economic instruments (EI) were also studied. The findings revealed that the provisions of the legal instruments are not strong and clear enough to compel states to adopt adequate measures for the prevention of toxic oxyanion pollutants in marine areas. In addition, even though the CAC and EI approaches have been adopted for pollution abatement across countries, the latter appear to have gained wider acceptance, due to some of the advantages it offers over and above the former approach. Nevertheless, the chapter recommends the combination of regulatory and economic approaches as the way forward in achieving the abatement of toxic oxyanion in aqua systems. One of the recommended regulatory approaches is the amendment of existing treaties and instruments to incorporate stronger obligations on states, which will feasibly achieve effective measures for the reduction and control of toxic oxyanion pollutants. The justification for the eco-legal approach to control toxic oxyanion pollutants is to yield the best optimal outcome because none of the instruments can operate in isolation, especially in a dynamic and complex society. Both, complement and reinforce each other.
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Nitrate is one of the most widespread toxic inorganic compounds in groundwater due to its high water solubility. High level of nitrate in potable water may poses serious risks to the environment and to human health. Heterogeneous photocatalysis has been widely used for water remediation and disinfection, however, less research studies, comparatively, have reported photocatalytic nitrate reduction because of the complexity of the mechanism of reaction. Mainly, nitrate photoreduction takes place directly via reaction with photo-generated electrons in the conduction band of the photocatalyst or by photo-produced reducing species under light irradiation. As a result, nitrate can be transformed into unpreferred by-products such as nitrite and ammonium, while the reduction into dinitrogen gas is much recommended due to its high importance. On the other hand, the issue of the re-oxidation of ammonium into nitrate has also been reported. The efficiency and selectivity of a photocatalytic system to reduce nitrate into dinitrogen depend on the operating parameters controlling the reaction, and more importantly, the selectivity strongly depends on the type of the photocatalytic nanomaterial. For this reason, a pool of studies have been performed in order to enhance the selectivity of nitrate reduction into dinitrogen by developing different kinds of nanomaterials. In this chapter, we examine: (i) the conventional technologies for nitrate removal/reduction, (ii) the effect of operating conditions on the photocatalytic nitrate reduction process, as well as (iii) the influence of the type of photoactive nanomaterial on the selectivity and the performance toward nitrate reduction.
Chapter
Global developmental strategies and population expansion are continuously showing their odd impacts on the living world, thereby causing stresses of multiple natures. To combat these stresses, hydrogen sulfide (H2S) is well-examined signaling molecule that acts as a priming agent and helps in regulating the response of plants to various stressful conditions. Hydrogen sulfide is formed in the plant cells as an intermediate of an assimilatory sulfate reduction. Despite the endogenous release of hydrogen sulfide, its exogenous application has been found to be beneficial in the amelioration of multiple abiotic stresses. These responses are also mediated by the expression of genes and proteins that participate in signaling and metabolic pathways induced through several small signaling molecules known as plant hormones or phytohormones. Phytohormones are also found to be involved in regulation of the protective responses under various abiotic and biotic stress conditions. H2S in crosstalk with these phytohormones significantly ameliorates the abiotic stress in plants. In this chapter we have discussed in detail how H2S in crosstalk with phytohormones helps in the enhancement of defense against abiotic stress in plants.
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The effects of thyroid hormones on female gonadal functions are well established. The role of thyroid hormones in testicular physiology is still uncertain, and so the effect of hypothyroidism on the testicular functions was investigated in postnatal rats. Hypothyroidism was induced during postnatal life by adding methimazole to the drinking water of lactating mothers starting from the day of birth. On day 25 the rats were sacrificed and testis, epididymis, seminal vesicles and ventral prostate were collected. A reduction in the body weight and the weights of testis, epididymis and accessory sex organs of treated rats was recorded. The levels of all the biochemical parameters in the testis, e.g. protein, RNA, ascorbic acid, acid phosphatase, alkaline phosphatase and isocitrate dehydrogenase, were reduced following methimazole treatment. The results indicated decreased bioavailability of androgens in hypothyroid rats and an inhibition of testicular functions. The results suggest that thyroid hormones are necessary for normal testicular functions.
Article
The selenoenzyme phospholipid hydroperoxide glutathione peroxidase (PHGPx, EC 1.11.1.12) is present, in both free and membrane-bound form, in several mammalian tissues. It utilizes thiols such as glutathione to specifically scavenge phospholipid hydroperoxides. The testis exhibits the highest PHGPx-specific activity so far measured, and interest in the presence and function of the enzyme in this tissue has recently grown. Here we report the localization of PHGPx in rat epididymal spermatozoa and its distribution in subfractions obtained by sucrose density gradient centrifugation. Immunochemical evidence and enzymatic activity revealed for the first time that PHGPx is present in sperm heads and tail midpiece mitochondria. The binding of the enzyme to spermatozoa, head, and mitochondria was barely affected by ionic strength or thiols or detergents, as compared to the detachment of PHGPx obtained from testis nuclei. Moreover, we demonstrated that pure PHGPx exhibits a higher thiol-oxidase activity toward isolated epididymal caput protamines than toward protamines from epididymal cauda. These results suggest a role for the enzyme in the maturation of spermatozoa through the metabolism of hydroperoxides and sperm thiol oxidation, in addition to its serving as an antioxidant protector.