Interactions between polymorphisms in the aryl hydrocarbon receptor signalling pathway and exposure to persistent organochlorine pollutants affect human semen quality.
Persistent
organic
pollutants
(POPs)
may
affect
male
reproductive
function.
Many
dioxin-like
POPs
exert
their
effects
by
activation
of
the
aryl
hydrocarbon
receptor
(AHR)
signalling
pathway.
We
analysed
whether
gene–environment
interactions
between
polymorphisms
in
AHR
(R554K)
and
AHR
repressor
(AHRR
P185A)
and
serum
levels
of
markers
of
POP
exposure
1,1-bis-(4-chlorophenyl)-2,2-dichloroethene
(
p,p
-DDE)
and
2,2
,4,4
,5,5
-hexachlorobiphenyl
(CB-153)
are
associated
with
21
parameters
of
male
reproductive
function
in
581
proven-fertile
European
and
Greenlandic
men.
In
Greenlandic
men,
AHR
variants
significantly
modified
the
association
between
serum
levels
of
both
p,p
-DDE
and
CB-153
and
inhibin
B
levels,
sperm
chromatin
integrity,
and
seminal
zinc
levels.
In
the
total
cohort,
interactions
between
AHRR
variants
and
serum
levels
of
CB-153
were
associated
with
sperm
chromatin
integrity
and
the
expression
of
the
pro-apoptotic
marker
protein
Fas.
The
data
indicate
that
susceptibility
to
adverse
effects
of
POP
exposure
on
male
reproductive
function
is
dependent
on
polymorphisms
in
genes
involved
in
AHR
signallin
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