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Exposure to persistent organic pollutants and sperm sex chromosome ratio in men from the Faroe Islands
People in the Arctic as well as fishermen on the polluted Swedish east coast are highly exposed to persistent organic pollutants (POPs). These compounds have been shown to affect the sperm Y:X chromosome ratio. In present study, the aim was to investigate whether polychlorinated biphenyl (PCB) congeners and 1,1,-dichloro-2,2,-bis(p-chlorophenyl)ethane (p,p′-DDE) influence sperm sex chromosome ratio in Faroese men, and whether these men differ regarding Y:X ratio compared to Greenland Inuit and Swedish fishermen.
The study population (n = 449) consisted of young men from the general population (n = 276) as well as proven fertile men (n = 173). The Y:X ratio was assessed by fluorescent in situ hybridization. Serum concentrations of POPs were measured using gas chromatography. Associations between POP concentrations and Y:X ratio were calculated using linear and non-linear regression models as well as trend analysis and pairwise comparison of exposure data categorized into quartiles.
The selected POPs were associated with Y:X ratio in fertile Faroese men, but not in the total population; p,p′-DDE (95% CI for B = − 0.005 to − 0.001, p = 0.005) and ΣPCB (95% CI for B = − 0.005 to − 0.001, p = 0.012). Since p,p′-DDE and ΣPCB correlated significantly (r = 0.927, p < 0.001), the results involving the exposure variables can be regarded as a single finding. The Y:X ratio for the total Faroese population was 0.500 ± 0.018, which was statistically significantly lower than in both Inuit and Swedish fishermen (0.512 for both).
In conclusion, Faroese men presented with lower Y:X ratio than Greenland Inuit and Swedish fishermen. Although no direct health effects are expected due to the lower Faroese Y:X ratio, it could be indicative of adverse effects on the reproductive system
Non-linear association between androgen receptor CAG and GGN repeat lengths and reproductive parameters in fertile European and Inuit men
Exposure to persistent organic pollutants and sperm sex chromosome ratio in men from the Faroe Islands
More prevalent prescription of testosterone in men from couples undergoing intracytoplasmic sperm injection (ICSI)
17 Genetic variations in the androgen receptor gene in relation to PSA and prostate cancer diagnosis
Polymorphisms in genes regulating androgen activity among prostate cancer low-risk Inuit men and high-risk Scandinavians
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
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 signalling
Non-linear association between androgen receptor CAG and GGN repeat lengths and reproductive parameters in fertile European and Inuit men.
Recently the dogma that there is an inverse linear association between androgen receptor (AR) CAG and GGN polymorphisms and receptor activity has been challenged. We analysed the pattern of association between 21 male reproductive phenotypes and AR CAG/GGN repeat lengths in 557 proven-fertile men.A linear association was only found between sperm DNA fragmentation index (DFI) and CAG length, and between inhibin B and GGN length. Men with longer CAG then the reference (22-24), had higher oestradiol levels, whereas men with shorter CAG stretches had a higher DFI and a higher proportion of Fas-positive germ cells. Subjects with either short or long CAG had increased seminal levels of prostate-specific antigen and neutral α-glucosidase activity. Compared to men with the median GGN length of 23, those with shorter GGN repeats had higher levels of inhibin B, higher proportions of normal and progressive sperm, and a higher fraction of Fas-positive sperm, while men with longer GGN had higher oestradiol levels.These data indicate that at least for some markers of male reproductive function the association with CAG or GGN repeat length is curvilinear
Non-linear association between androgen receptor CAG and GGN repeat lengths and reproductive parameters in fertile European and Inuit men.
Recently the dogma that there is an inverse linear association between androgen receptor (AR) CAG and GGN polymorphisms and receptor activity has been challenged. We analysed the pattern of association between 21 male reproductive phenotypes and AR CAG/GGN repeat lengths in 557 proven-fertile men. A linear association was only found between sperm DNA fragmentation index (DFI) and CAG length, and between inhibin B and GGN length. Men with longer CAG then the reference (22-24), had higher oestradiol levels, whereas men with shorter CAG stretches had a higher DFI and a higher proportion of Fas-positive germ cells. Subjects with either short or long CAG had increased seminal levels of prostate-specific antigen and neutral α-glucosidase activity. Compared to men with the median GGN length of 23, those with shorter GGN repeats had higher levels of inhibin B, higher proportions of normal and progressive sperm, and a higher fraction of Fas-positive sperm, while men with longer GGN had higher oestradiol levels. These data indicate that at least for some markers of male reproductive function the association with CAG or GGN repeat length is curvilinear