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21 American Journal of Obstetrics & Gynecology JANUARY 2012 JANUARY 2012 American Journal of Obstetrics & Gynecology 21
www. AJOG.org Obstetrics Expert Reviews
play a pivotal role in reducing hydrogen man. 4,20
The content in food depends
peroxide (H2O2) and lipid peroxides to Dietary on the selenium content of the soil in
harmless products (water and alcohols; selenium which plants are grown or animals are
Figure 2), thereby dampening the prop- Plant foods are the major dietary raised. For example, the selenium
agation of damaging reactive oxygen sources of selenium in most content in the soil of the high plains of
16,17
species (ROS). As antioxidants, the countries.18,19 northern Nebraska and the Dakotas is
GPxs help maintain membrane integrity, Wheat is the most efficient selenium very high, and the inhabitants have the
protect prostacylin production, and ac- cumulator of the common highest selenium intakes in the United
limit the propagation of oxidative dam- cereals and is 1 of the most 21
States. Other foods make a substantial
age to lipids, lipoproteins, and deoxyri- important selenium sources for contribution to selenium intake in
17
bonucleic acid (DNA). northern Europe, particularly meat,
Of particular importance to reproduc- poultry, and fish (a total of about 36% in
22 American Journal of Obstetrics & Gynecology JANUARY 2012 JANUARY 2012 American Journal of Obstetrics & Gynecology 22
28
nancy and their lifetime. Dietary se-
FIGURE 1
lenium intake in most parts of Europe
Selenium metabolic pathway
Selenite is considerably lower than in the
General body proteins United States, mainly because of the
European soils providing a poorer
15,30
Selenoproteins source of selenium.
(as [Se]Cys/Sec) Assessments of requirements, ade-
GS-Se-SG
[Se]Met quacy, and intakes of selenium have
been reviewed previously in detail15,30
and summarized in Table 2. Selenium
Selenophosphate GS-SeH
intake appears on average to be at or
[Se]Cys/Sec
above the recommended dietary intakes
in the United States (60-220
19,31,32
H2Se g/d) or Canada (50-200
33,34
g/d). However, modest selenium
deficiency, in associa- tion with poor
CH3SeH diet, has been described in the United
States among the poor and obese,
which a recent review links pro-
(CH3)2Se Breath spectively to cardiovascular disease and
35
immune dysfunction. In the United
Kingdom, selenium dietary intake is
generally below the reference nutrient
+
intakes (30-40 g/d).22,36,37
(CH3)3Se Urine and Faeces
This diagram illustrates how selenoproteins can be produced in the body from a variety of selenium Selenium toxicity
sources. Glutathione (GSH) is considered to be the main component of the selenium metabolism There is also a moderate to high health
pathway, taking part in the first of a series of reduction reactions that convert selenite to hydrogen risk of selenium toxicity, first
selenide (H2Se), which is regarded as the precursor for supplying selenium in an active form for discovered in animals grazing in areas
synthesis of selenoproteins. The further metabolism of H2Se involves sequential methylation to methyl- with high se- lenium content in the
selenide (CH3SeH), dimethylselenide ([CH3]2Se), trimethylselenonium ion ((CH3)3Se ). soil.38 Chronic toxicity of selenium in
[Se]Met, selenomethionine; [Se]Cys, selenocysteine. humans results in selenosis, a
Adapted from other sources.5,6,158 condition characterized by brittleness
Mistry. Selenium in reproductive health. Am J Obstet Gynecol or loss of hair and nails,
2012. gastrointestinal problems, rashes, gar-
lic breath odor, and nervous system
39
abnormalities.
the United Kingdom).22 Thus, it has Selenium deficiency In China, it has been reported that
been predicted that vegetarians or veg- Selenium deficiency as assessed by di- sel- enosis occurs with increased
ans are at specific risk of selenium defi- etary intake and/or blood selenium con- frequency in people who consumed
4,23
ciency, but this claim is not fully centrations has been identified in selenium at levels above 850 g/d.40
substantiated. people inhabiting geographical regions The Institute of Medicine (United
Selenium incorporation into plants, notable for low soil selenium content, States) has set a toler- able upper
and then into animal tissues, depends on such as volcanic regions.15,25 Human intake level for selenium at
selenium 400 g/d for adults to prevent the risk of
not only soil selenium content or geo- developing selenosis.41 The European
deficiency diseases have been recognized Commission and the World Health Or-
chemistry but also soil pH, rainfall, in China and Tibet. 26,27 Keshan disease,
land ganization have proposed the lower daily
contour, and the use of high-sulphur fer-
However, in wetter regions, a reversible endemic cardiomyopathy, is
4,20
tilizers. Some bacteria can convert plexes.
insol- uble forms of selenium to soluble 4 characterised by focal myocardial necro-
rain leaches selenium from the soil.
forms, which can then be taken up by sis often associated with inflammatory
20,24
plants. Se- lenium tends to be infiltrates and calcification.
concentrated in the soils of the drier The disorder is exclusively endemic in
28
regions of the world, in which soil is selenium-deficient rural areas of China
usually more alkaline; in acidic poorly and supplementation with selenium
aerated soils, selenium is rel- atively tablets (such as sodium selenite) in
unavailable to plants because it is 29
pregnancy provides highly effective
present mainly as insoluble selenite com-
protection against its development in upper limit of 300 g/d for Selenium is essential for testosterone
susceptible women, both during preg- adults.
42,43 biosynthesis and the formation and nor-
44,45
mal development of spermatozoa.
Selenium in reproductive Testicular tissue contains high concen-
health trations of selenium, predominantly as
Male GPx4, and this provides the link
fertility between selenium, sperm quality, and
male fertil-
ity because GPx4 is a fundamental deter- TABLE 1
minant of the architecture of the sperma- Known mammalian selenoproteins that carry out functions
14,18
tozoan midpiece14,46 and is considered to of selenium (adapted from elsewhere )
shield developing sperm cells from oxida- Selenoprotein Proposed function
47,48
tive DNA damage. ROS have been GPx.....................................................................................................................................................................................................................................
implicated in male infertility because,
GPx1 Antioxidant in cell cytosol; Se store?
through attack of the spermatozoa mem- .....................................................................................................................................................................................................................................
Some evidence suggests that increas- GPx3 Antioxidant in extracellular space and plasma
.....................................................................................................................................................................................................................................
ing selenium dietary intake increases GPx4 Antioxidant in membranes; structural protein in sperm;
an- tioxidant GPx activity, thereby apoptosis?
.....................................................................................................................................................................................................................................
49
increas- ing male fertility. The study in GPx5 Unknown
.....................................................................................................................................................................................................................................
50
1984 by Bleau et al reported an GPx6 GPx1 homolog?
..............................................................................................................................................................................................................................................
optimal range between 50 and 60 Thioredoxin reductase (TR) Multiple roles including dithiol-disulphide oxoreductase.
g/mL in semen and a positive Detoxifies peroxides, reduces thioredoxin (control of cell
correlation between sperm count and growth); maintains redox state of transcription factors
.....................................................................................................................................................................................................................................
semen selenium concentra- tion in 125 TR1 Mainly cystosolic, ubiquitous
.....................................................................................................................................................................................................................................
men from couples being in- vestigated TR2 Expressed by testes
.....................................................................................................................................................................................................................................
for infertility. TR3 Mitochondrial, ubiquitous
In Scotland, a placebo-controlled ran- ..............................................................................................................................................................................................................................................
Iodothyronine deiodinases
domized control trial (RCT) of 64 men .....................................................................................................................................................................................................................................
Types D1 and D2 Converts thyroxine (T4) to bioactive 3,5,3-tri-iodothyronine
demonstrated that sperm quality and
fertility improved after selenium supple-
mentation.51 Other placebo-controlled
52 48
RCTs from Tunisia and Iran of infer-
(T3)
tile men demonstrated the beneficial ef- ...............................................................................................................................
men with idiopathic asthenoteratosper- 15 kDa selenoprotein (Sep 15) Protects against cancer?
..............................................................................................................................................................................................................................................
no information on parity or interpreg- vestigated in relation to preeclampsia. as well as cord blood and placental tissue
64
nancy intervals are provided, which Selenoprotein S (also known as collected immediately after delivery. To-
could confound the results. Early SEPS1 or VIMP), which contains a Sec
pregnancy loss has been linked to residue at its active site, is an
reduced antioxidant protection of antiinflammatory protein that acts
biological membranes and DNA and primarily to limit the damaging
also to low concentrations of the GPx,76- consequences of endoplasmic reticulum
78 90
warranting further investiga- tions to stress. It has recently been suggested
establish whether women with re- current to contribute to the develop- ment of
pregnancy loss could potentially benefit 91
preeclampsia. A polymorphic variant
from the optimization of selenium status. in the SEPS1 locus has been asso- ciated
with increased cardiovascular dis- ease
Preeclampsia morbidity in Finnish females and a
92