Reproductive and Developmental Toxicity of Metals - Toxicology of Metals - page 211

Recent evidence indicates that the human male repro-
ductive capacity has deteriorated considerably dur-
ing the past fi ve decades. In industrialized countries,
a substantial number of couples seek in vitro fertiliza-
tion (IVF) or intracytoplasmic sperm injection (ICSI)
because of poor semen quality.
Furthermore, large differences in mean sperm con-
centration between countries, and between different
locations within a country, have been observed. The
possible role of environmental and lifestyle factors in
contributing to these trends and differences has been
suggested and is widely debated, because considera-
tion must be given to many potentially confounding
factors. Because the underlying causes are likely to
be multiple and complex, it is important to identify the
factors contributing to the deterioration of human male
fertility to prevent further decline in fertility potential.
The human male has a relatively low fertility poten-
tial compared with other mammals. For example, the
number of sperm per human ejaculate is typically only
twofold to fourfold higher than the number at which
fertility is signifi cantly reduced, whereas the number
of sperm in rat, rabbit, or bull ejaculate is many times
(up to 1400-fold) the number that will produce maxi-
mum fertility (Working, 1988). Human males have
markedly smaller relative testis size and the lowest
rate of daily sperm production per gram of testis, by
a factor of more than 3, compared with mouse, rat,
or monkey. The percentages of progressively motile
sperm and morphologically normal sperm in human
semen are also considerably lower than in experimen-
tal animals (Working, 1988). Certain rodent species
and strains, commonly used in experimental studies,
seem to be resistant to the male reproductive toxicity
of lead (Apostoli et al ., 1998) and cadmium (Gunn et
al ., 1965; Liu et al., 2001). The human male may be
more susceptible than the rat to metal toxicity, pos-
sibly because of poorer effi cacy of the antioxidant
defense system and greater vulnerability to oxidative
damage to sperm DNA and sulfhydryl (-SH) groups
required for the maintenance of sperm maturation
and motility. Because of differences among species in
reproductive endpoints and in the route, level, and
duration of metal exposure, the experimental animal
data may be useful for estimates of allowable human
exposure.
Although experimental animal and in vitro stud-
ies have indicated adverse reproductive effects of
high doses of many metals and benefi cial or protec-
tive effects of some essential metals (particularly zinc,
selenium, and magnesium), the internal metal dose
was often not measured, and relatively few studies
have evaluated the effects of long-term moderate oral
exposure. For most metals, data relevant to humans

are scanty and are usually limited by inadequate con-
trols and adjustments for the infl uence of potentially
confounding variables.

2.1 Lead
Since the mid-19th century, many studies have
shown the toxicity of lead on male reproductive func-
tion in humans and experimental animals, although
the impact of low to moderate levels of chronic lead
exposure is still controversial. A recent comprehen-
sive review presents the relevant literature (Apostoli
et al ., 1998), and, therefore, the subsequently published
evidence is emphasized here.
Several studies of men occupationally exposed
to lead have shown that blood lead levels equal to
400 g/L were associated with signifi cantly reduced

semen quality, whereas reproductive endocrine func-
tion in the same subjects was either not affected or
was only marginally affected (Alexander et al ., 1996b;
Assennato et al ., 1986; Cullen et al ., 1984; Lancranjan
et al ., 1975; Telišman et al ., 2000). Other studies that
measured only sex hormones have generally shown
no relevant lead effect on male reproductive endo-
crine profi le (Erfurth et al., 2001; Gennart et al., 1992a;
Gustafson et al., 1989; McGregor and Mason, 1990; Ng
et al ., 1991). For example, a Swedish study of 62 active
and 15 retired lead workers and 26 control subjects
(Erfurth et al., 2001) showed no signifi cant association
between either blood lead, serum lead, or fi ng er bone
lead levels and serum levels of follicle-stimulating
hormone (FSH), luteinizing hormone (LH), testoster-
one, and sex-hormone binding globulin; the median
and range blood lead values in the subgroups were
332 (83-932)

µ

µ g/L, 186 (104-497) µ g/L, and 41 (8-62)

µ g/L, respectively.

The following lead-related effects on human semen
quality have been reported: a decrease in semen vol-
ume (Fisher-Fischbein et al ., 1987; Lerda, 1992; Wildt
et al ., 1983), a decrease in sperm concentration and
sperm count (Alexander et al ., 1996a; Assennato et
al ., 1986; Braunstein et al ., 1978; Cullen et al ., 1984;
Fisher-Fischbein et al ., 1987; Lancranjan et al ., 1975;
Lerda, 1992), a decrease in sperm motility (Chia et al .,
1992; Cullen et al ., 1984; Lancranjan et al ., 1975; Lerda,
1992; Viskum et al ., 1999), and in the quality of motil-
ity (Fisher-Fischbein et al ., 1987; Viskum et al ., 1999),
an increase in abnormal sperm morphology (Cullen
et al., 1984; Fisher-Fischbein et al ., 1987; Lancranjan
et al ., 1975; Lerda, 1992; Wildt et al ., 1983), particularly
at the head of the sperm (Fisher-Fischbein et al ., 1987;
Lerda, 1992; Wildt et al., 1983), and impairment of pros-
tate secretory function as indicated by decreased semi-
nal plasma zinc level (Wildt et al ., 1983). Most of these