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1.  Prognostic factors in lumbar spinal stenosis surgery 
Acta Orthopaedica  2012;83(5):536-542.
Background and purpose
A considerable number of patients who undergo surgery for spinal stenosis have residual symptoms and inferior function and health-related quality of life after surgery. There have been few studies on factors that may predict outcome. We tried to find predictors of outcome in surgery for spinal stenosis using patient- and imaging-related factors.
Patients and methods
109 patients in the Swedish Spine Register with central spinal stenosis that were operated on by decompression without fusion were prospectively followed up 1 year after surgery. Clinical outcome scores included the EQ-5D, the Oswestry disability index, self-estimated walking distance, and leg and back pain levels (VAS). Central dural sac area, number of levels with stenosis, and spondylolisthesis were included in the MRI analysis. Multivariable analyses were performed to search for correlation between patient-related and imaging factors and clinical outcome at 1-year follow-up.
Results
Several factors predicted outcome statistically significantly. Duration of leg pain exceeding 2 years predicted inferior outcome in terms of leg and back pain, function, and HRLQoL. Regular and intermittent preoperative users of analgesics had higher levels of back pain at follow-up than those not using analgesics. Low preoperative function predicted low function and dissatisfaction at follow-up. Low preoperative EQ-5D scores predicted a high degree of leg and back pain. Narrow dural sac area predicted more gains in terms of back pain at follow-up and lower absolute leg pain.
Interpretation
Multiple factors predict outcome in spinal stenosis surgery, most importantly duration of symptoms and preoperative function. Some of these are modifiable and can be targeted. Our findings can be used in the preoperative patient information and aid the surgeon and the patient in a shared decision making process.
doi:10.3109/17453674.2012.733915
PMCID: PMC3488183  PMID: 23083437
2.  A Nested Case-Control Study of Intrauterine Exposure to Persistent Organochlorine Pollutants and the Risk of Hypospadias 
PLoS ONE  2012;7(9):e44767.
Background
Environmental exposures to endocrine disrupting chemicals have been suggested as a risk factor for male genital abnormalities such as hypospadias. The aim of this case-control study was to investigate the association between fetal exposure to persistent organochlorine pollutants (POP) and the risk for hypospadias.
Methodology/Principal Findings
The Southern Sweden Maternity Cohort (SSMC) contains serum samples collected in early pregnancy among women in Southern Sweden. Linkages with the Medical Birth Register, the Malformation Register and the In-patient Register resulted in 390 SSMC mothers who had given birth to a boy with hypospadias in year 1986–2002 (mean 1995). For 237 of these (cases) sufficient amounts of serum for the chemical analyses were available. For each case, a control boy from the SSMC was randomly selected, matched for maternal age, birth year, parity and maternal smoking. PCB-153, p,p’-DDE and hexachlorbenzene (HCB) were used as biomarkers for POP exposure. The exposures were categorized into quartiles based on the distributions among the controls. There were no statistically significant trends between the a priori categorisation of the exposure variables and the risk for hypospadias. However, when the upper HCB quartile (>26 ng/ml) was compared to the other quartiles an odds ratio of 1.65 (95% CI 1.02 to 2.69) was obtained. p,p′-DDE levels above median (>1.0 ng/ml) compared to levels below 0.1 ng/ml gave an OR of 1.69 (95% CI 0.97 to 2.93).
Conclusions
The present study suggests that fetal exposure to HCB and p,p’-DDE may be a risk factor for hypospadias.
doi:10.1371/journal.pone.0044767
PMCID: PMC3459969  PMID: 23028613
3.  Phthalates and Perfluorooctanesulfonic Acid in Human Amniotic Fluid: Temporal Trends and Timing of Amniocentesis in Pregnancy 
Environmental Health Perspectives  2012;120(6):897-903.
Background: Measures of prenatal environmental exposures are important, and amniotic fluid levels may directly reflect fetal exposures during hypothesized windows of vulnerability.
Objectives: We aimed to detect various phthalate metabolites and perfluorooctanesulfonic acid (PFOS) in human amniotic fluid, to study temporal exposure trends, and to estimate potential associations with gestational week of amniocentesis and maternal age and parity at amniocentesis.
Methods: We studied 300 randomly selected second-trimester amniotic fluid samples from a Danish pregnancy-screening biobank covering 1980 through 1996. We used only samples from male offspring pregnancies. We assayed the environmental pollutants by liquid chromatography/triple quadrupole mass spectrometry and analyzed data using generalized linear regression models.
Results: We detected the di(2-ethylhexyl) phthalate (DEHP) metabolite mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP) at a median concentration of 0.27 ng/mL [interquartile range (IQR): 0.20–0.37 ng/mL], the diisononyl phthalate (DiNP) metabolite mono(4-methyl-7-carboxyheptyl) phthalate (7cx-MMeHP) at 0.07 ng/mL (IQR: 0.05–0.11 ng/mL), and PFOS at 1.1 ng/mL (IQR: 0.66–1.60 ng/mL). An increase of 1 calendar year was associated with 3.5% lower [95% confidence interval (CI): –4.8%, –2.1%] 5cx-MEPP levels and with 7.1% higher (95% CI: 5.3%, 9.0%) 7cx-MMeHP levels. For each later gestational week of amniocentesis, 5cx-MEPP was 9.9% higher (95% CI: 4.8%, 15.2%), 7cx-MMeHP was 8.6% higher (95: CI: 2.7%, 14.9%), and PFOS was 9.4% higher (95: CI: 3.3%, 15.9%). We observed no associations with maternal age or parity.
Conclusions: Measured metabolite levels appeared to parallel decreasing DEHP exposure and increasing DiNP exposure during the study period. The environmental pollutant levels were positively associated with later gestational age at amniocentesis during pregnancy weeks 12–22.
doi:10.1289/ehp.1104522
PMCID: PMC3385442  PMID: 22398305
amniocentesis; amniotic fluid; biobank; biomonitoring; perfluorinated compounds; phthalates; pregnancy; temporal trend
4.  Association between Pregnancy Loss and Urinary Phthalate Levels around the Time of Conception 
Environmental Health Perspectives  2011;120(3):458-463.
Background: Animal studies indicate that some phthalate metabolites may harm female reproductive function.
Objectives: We assessed the associations between exposure to phthalate metabolites and pregnancy loss.
Methods: Using a previously established cohort of couples planning their first pregnancy, we analyzed four primary and two oxidized secondary phthalate metabolites in urine samples collected on day 10 after the first day of the last menstrual period before conception occurred (n = 128) and during the previous cycle (if any, n = 111). Subclinical embryonal loss was identified by repeated measurement of urinary human chorionic gonadotropin, and information on clinical spontaneous abortions was obtained by telephone interview with the mother.
Results: Pregnancy loss (n = 48) was increased among women with urinary concentration of monoethylhexyl phthalate (MEHP) in the upper tertile in the conception sample compared with women in the lowest tertile [adjusted odds ratio (OR) = 2.9; 95% confidence interval (CI): 1.1, 7.6]. The corresponding OR for subclinical embryonal loss (n = 32) was 40.7 (95% CI: 4.5, 369.5).
Conclusions: The phthalate metabolite MEHP was associated with higher occurrence of pregnancy loss. Because this is the first human study to show this association and the sample size is small, the findings need to be corroborated in independent studies.
doi:10.1289/ehp.1103552
PMCID: PMC3295336  PMID: 22113848
abortion; MEHP; phthalates; pregnancy loss
5.  Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study 
BMC Cancer  2011;11:381.
Background
Serum protein profiles have been investigated frequently to discover early biomarkers for breast cancer. So far, these studies used biological samples collected at or after diagnosis. This may limit these studies' value in the search for cancer biomarkers because of the often advanced tumor stage, and consequently risk of reverse causality. We present for the first time pre-diagnostic serum protein profiles in relation to breast cancer, using the Prospect-EPIC (European Prospective Investigation into Cancer and nutrition) cohort.
Methods
In a nested case-control design we compared 68 women diagnosed with breast cancer within three years after enrollment, with 68 matched controls for differences in serum protein profiles. All samples were analyzed with SELDI-TOF MS (surface enhanced laser desorption/ionization time-of-flight mass spectrometry). In a subset of 20 case-control pairs, the serum proteome was identified and relatively quantified using isobaric Tags for Relative and Absolute Quantification (iTRAQ) and online two-dimensional nano-liquid chromatography coupled with tandem MS (2D-nanoLC-MS/MS).
Results
Two SELDI-TOF MS peaks with m/z 3323 and 8939, which probably represent doubly charged apolipoprotein C-I and C3a des-arginine anaphylatoxin (C3adesArg), were higher in pre-diagnostic breast cancer serum (p = 0.02 and p = 0.06, respectively). With 2D-nanoLC-MS/MS, afamin, apolipoprotein E and isoform 1 of inter-alpha trypsin inhibitor heavy chain H4 (ITIH4) were found to be higher in pre-diagnostic breast cancer (p < 0.05), while alpha-2-macroglobulin and ceruloplasmin were lower (p < 0.05). C3adesArg and ITIH4 have previously been related to the presence of symptomatic and/or mammographically detectable breast cancer.
Conclusions
We show that serum protein profiles are already altered up to three years before breast cancer detection.
doi:10.1186/1471-2407-11-381
PMCID: PMC3189190  PMID: 21871081
Biomarkers; Breast cancer; Early diagnosis; 2D-nanoLC-MS/MS; Prospective; Proteomics; SELDI-TOF MS
6.  Correlation between disability and MRI findings in lumbar spinal stenosis 
Acta Orthopaedica  2011;82(2):204-210.
Background and purpose
MRI is the modality of choice when diagnosing spinal stenosis but it also shows that stenosis is prevalent in asymptomatic subjects over 60. The relationship between preoperative health-related quality of life, functional status, leg and back pain, and the objectively measured dural sac area in single and multilevel stenosis is unknown. We assessed this relationship in a prospective study.
Patients and methods
The cohort included 109 consecutive patients with central spinal stenosis operated on with decompressive laminectomy or laminotomy. Preoperatively, all patients completed the questionnaires for EQ-5D, SF-36, Oswestry disability index (ODI), estimated walking distance and leg and back pain (VAS). The cross-sectional area of the dural sac was measured at relevant disc levels in mm2, and spondylolisthesis was measured in mm. For comparison, the area of the most narrow level, the number of levels with dural sac area < 70 mm2, and spondylolisthesis were studied.
Results
Before surgery, patients with central spinal stenosis had low HRLQoL and functional status, and high pain levels. Patients with multilevel stenosis had better general health (p = 0.04) and less leg and back pain despite having smaller dural sac area than patients with single-level stenosis. There was a poor correlation between walking distance, ODI, the SF-36, EQ-5D, and leg and back pain levels on the one hand and dural sac area on the other. Women more often had multilevel spinal stenosis (p = 0.05) and spondylolisthesis (p < 0.001). Spondylolisthetic patients more often had small dural sac area (p = 0.04) and multilevel stenosis (p = 0.06).
Interpretation
Our findings indicate that HRQoL, function, and pain measured preoperatively correlate with morphological changes on MRI to a limited extent.
doi:10.3109/17453674.2011.566150
PMCID: PMC3235292  PMID: 21434811
7.  Dural lesions in lumbar disc herniation surgery: incidence, risk factors, and outcome 
European Spine Journal  2009;19(3):439-442.
In lumbar disc herniation surgery, dural lesions seem to be the most common complication today. Studies on incidence of and outcome after a dural lesion are mainly based on retrospective studies. In a prospective study within the framework of the Swedish Spine Register, 4,173 patients operated on for lumbar disc herniation were evaluated using pre- and 1-year postoperative protocols and complication registration. Mean patient age was 41 (18–81) years and 53% of the patients were male. 93% of the operations were performed on the two lowermost lumbar levels. The incidence of dural lesions in the material was 2.7%. In patients with previous disc surgery, the incidence was doubled, 5%, a significant increase (P = 0.02). Patients with dural lesions preoperatively had more back pain and inferior scores in general health and role emotional domains of the SF-36. These factors, however, were because they had been operated on previously, not related to the dural lesion as such. The relative improvement after surgery was similar whether a dural lesion had occurred or not. It is concluded that a dural lesion is a technical complication which must be solved at the time of surgery but which does not bear any negative implications on the long-term outcome for the patient.
doi:10.1007/s00586-009-1236-x
PMCID: PMC2899750  PMID: 20013002
Lumbar disc herniation; Complication; Surgery; Outcome
8.  TRPV1 in Brain Is Involved in Acetaminophen-Induced Antinociception 
PLoS ONE  2010;5(9):e12748.
Background
Acetaminophen, the major active metabolite of acetanilide in man, has become one of the most popular over-the-counter analgesic and antipyretic agents, consumed by millions of people daily. However, its mechanism of action is still a matter of debate. We have previously shown that acetaminophen is further metabolized to N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z -eicosatetraenamide (AM404) by fatty acid amide hydrolase (FAAH) in the rat and mouse brain and that this metabolite is a potent activator of transient receptor potential vanilloid 1 (TRPV1) in vitro. Pharmacological activation of TRPV1 in the midbrain periaqueductal gray elicits antinociception in rats. It is therefore possible that activation of TRPV1 in the brain contributes to the analgesic effect of acetaminophen.
Methodology/Principal Findings
Here we show that the antinociceptive effect of acetaminophen at an oral dose lacking hypolocomotor activity is absent in FAAH and TRPV1 knockout mice in the formalin, tail immersion and von Frey tests. This dose of acetaminophen did not affect the global brain contents of prostaglandin E2 (PGE2) and endocannabinoids. Intracerebroventricular injection of AM404 produced a TRPV1-mediated antinociceptive effect in the mouse formalin test. Pharmacological inhibition of TRPV1 in the brain by intracerebroventricular capsazepine injection abolished the antinociceptive effect of oral acetaminophen in the same test.
Conclusions
This study shows that TRPV1 in brain is involved in the antinociceptive action of acetaminophen and provides a strategy for developing central nervous system active oral analgesics based on the coexpression of FAAH and TRPV1 in the brain.
doi:10.1371/journal.pone.0012748
PMCID: PMC2941447  PMID: 20862299
9.  Association of maternal serum concentrations of 2,2', 4,4'5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) levels with birth weight, gestational age and preterm births in Inuit and European populations 
Environmental Health  2010;9:56.
Background
Epidemiological studies on the association between maternal exposure to persistent organic pollutants (POPs) and fetal growth alteration report inconsistent findings which weights in favor of additional studies.
Methods
Blood samples were collected from interviewed pregnant women in Greenland (572), Kharkiv (611) and Warsaw (258) and were analyzed for CB-153 and p,p'-DDE by gas chromatography-mass spectrometry. Data on birth weight, gestational age and preterm birth were obtained for 1322 singleton live births. We examined the association between natural log-transformed serum POPs concentration and birth weight and gestational age using multiple linear regression and the association with prematurity using logistic regression controlling for potential confounding factors.
Results
The median serum concentrations of CB-153 and p,p'-DDE were for Inuit mothers 105.6 and 298.9, for Kharkiv mothers 27.0 and 645.4 and for Warsaw mothers 10.7 and 365.2 ng/g lipids, respectively. Increase in CB-153 concentration by one unit on the log scale in Inuit mothers serum was associated with significant decrease in infant birth weight of -59 g and gestational age by -0.2 week. Decreases observed in the cohorts in Kharkiv (-10 g and -0.1 week) and in Warsaw (-49 g and -0.2 week) were not statistically significant. Increase in p,p'-DDE concentration by one unit on the log scale was associated with a statistically significant decrease in infant birth weight of -39.4 g and -104.3 g and shortening of gestational age of -0.2 week and -0.6 week in the Inuit and Warsaw cohorts, respectively. In the Kharkiv cohort decrease in birth weight (-30.5 g) was not significant, however a shortening of gestational age of -0.2 week per increase in p,p'-DDE concentration by one unit on the log scale was of the borderline significance. There was no significant association between CB-153 and p,p'-DDE concentrations and risk of preterm birth however, in all cohorts the odds ratio was above 1.
Conclusions
In utero exposure to POPs may reduce birth weight and gestational age of newborns however, new insights as to why results vary across studies were not apparent.
doi:10.1186/1476-069X-9-56
PMCID: PMC2944244  PMID: 20819217
10.  A Nested Case-Control Study of Intrauterine Exposure to Persistent Organochlorine Pollutants in Relation to Risk of Type 1 Diabetes 
PLoS ONE  2010;5(6):e11281.
Background
The incidence of type 1 diabetes in Europe is increasing at a rate of about 3% per year and there is also an increasing incidence throughout the world. Type 1 diabetes is a complex disease caused by multiple genetic and environmental factors. Persistent organochlorine pollutants (POPs) have been suggested as a triggering factor for developing childhood type 1 diabetes. The aim of this case-control study was to assess possible impacts of in utero exposure to POPs on type 1 diabetes.
Methodology/ Principal Findings
The study was performed as a case-control study within a biobank in Malmö, a city located in the Southern part of Sweden. The study included 150 cases (children who had their diagnosis mostly before 18 years of age) and 150 controls, matched for gender and day of birth. 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153) and the major DDT metabolite 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p′-DDE) were used as a biomarkers for POP exposure. When comparing the quartile with the highest maternal serum concentrations of PCB-153 with the other quartiles, an odds ratio (OR) of 0.73 (95% confidence interval [CI] 0.42, 1.27) was obtained. Similar results was obtained for p,p′-DDE (OR 0.56, 95% CI 0.29, 1.08).
Conclusions
The hypothesis that in utero exposure to POPs will trigger the risk for developing type 1 diabetes was not supported by the results. The risk estimates did, although not statistically significant, go in the opposite direction. However, it is not reasonable to believe that exposure to POPs should protect against type 1 diabetes.
doi:10.1371/journal.pone.0011281
PMCID: PMC2890585  PMID: 20585661
11.  Fetal loss and maternal serum levels of 2,2',4,4',5,5'-hexachlorbiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) exposure: a cohort study in Greenland and two European populations 
Environmental Health  2010;9:22.
Background
In the present study, the aim is to examine the risk of fetal loss related to environmental 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) or 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) exposure.
Methods
We related LC/MS/MS measurements of CB-153 and p,p'-DDE in serum samples to interview-data on previous fetal loss in populations of pregnant women from Poland, Ukraine and Greenland.
Results
In total, 1710 women were interviewed, and 678 of these had at least one previous pregnancy. The risk of ever experiencing a fetal loss increased at higher levels of CB-153 and p,p'-DDE exposure, with an adjusted odds ratio (OR) of 2.4; confidence interval (CI) (1.1-5.5) for CB-153>200 ng/g lipid compared to 0-25 ng CB-153/g lipid and OR of 2.5 CI (0.9-6.6) for p,p'-DDE>1500 ng/g lipid compared to 0-250 ng DDE/g lipid. However, no clear dose response associations were observed. The results further suggest that high level of organochlorine serum concentrations may be related to repeated loss.
Conclusions
The risk of fetal loss may increase at higher levels of CB-153 and p,p'-DDE exposure, although lack of dose response and inconsistencies between countries did not allow for firm conclusions.
doi:10.1186/1476-069X-9-22
PMCID: PMC2877014  PMID: 20459724
12.  The Swedish Spine Register: development, design and utility 
European Spine Journal  2009;18(Suppl 3):294-304.
The Swedish Spine Register enables monitoring of surgical activities focusing on changes in trends over time, techniques utilized and outcome, when implemented in general clinical practice. Basic requirements for a prosperous register are unity within the profession, mainly patient-based documentation and a well functioning support system. This presentation focuses on the development and design of the register protocol, problems encountered and solutions found underway. Various examples on how the results can be presented and utilized are given as well as validation. Register data demonstrate significant gender differences in lumbar disc herniation surgery with females having more pain, lower quality of life and more pronounced disability preoperatively while improvement after surgery is similar between genders. Quality of life after surgery for degenerative disorders is significantly improved for disc herniation, stenosis, spondylolisthesis and disc degenerative disorders. Over the last 10 years, surgical treatment for spinal stenosis has increased gradually while disc herniation surgery decreases regarding yearly number of procedures. An added function to the register enables more complex prospective clinical studies to include register data together with data suitable for the individual study. A common core set of demographic, surgical and outcome parameters would enable comparisons of clinical studies within and between nations.
doi:10.1007/s00586-009-1043-4
PMCID: PMC2899320  PMID: 19495812
Spine Register; Development; Degenerative lumbar spine; Core data set
13.  Fertility and Markers of Male Reproductive Function in Inuit and European Populations Spanning Large Contrasts in Blood Levels of Persistent Organochlorines 
Environmental Health Perspectives  2007;116(3):269-277.
Objective
We synthesized the main findings from an international epidemiologic study on the impact of biopersistent organic pollutants (POPs) on human reproductive function.
Data sources and extraction
We used a database with interview and biological data from 2,269 women and their spouses, and 18 published core papers.
Data synthesis
The study did not provide direct evidence of hormone-like activity of the polychlorinated biphenyl (PCB) congener CB-153 and the main dichlorodiphenyltrichloroethane (DDT) metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p′-DDE), as serum concentrations of these compounds were not consistently related to either endogenous or exogenous hormone activity in serum. Nevertheless several links bewteen POP exposure and biomarkers of male reproductive function were identified. First, an association between high CB-153 serum levels and low sperm counts was detected within a subgroup of men with short androgen receptor CAG repeat length. Second, a relationship between increased CB-153 serum concentrations and decreased sperm motility was seen in all four studied regions, and indications of reduced neutral α-glucosidase activity in seminal plasma point to a post-testicular effect. Third, damage of sperm chromatin integrity was considerably less frequent in Greenlandic Inuits compared with that in European groups, and only in the latter was impairment of sperm chromatin integrity related to POPs. Despite these effects, fertility in terms of time taken to conceive was not related to POPs except in Inuits. A likely explanation of the latter was not identified.
Conclusions
POPs may interfere with male reproductive function without major impact on fertility. The data do not provide direct evidence for endocrine disruption, hence other mechanisms should also be considered.
doi:10.1289/ehp.10700
PMCID: PMC2265036  PMID: 18335090
Inuit; polymorphisms; reproductive health; semen quality; sex hormone receptors; time to pregnancy; xenobiotics
14.  Xenoandrogenic Activity in Serum Differs across European and Inuit Populations 
Environmental Health Perspectives  2007;115(S-1):21-27.
Background
Animal and in vitro studies have indicated that human male reproductive disorders can arise as a result of disrupted androgen receptor (AR) signalling by persistent organic pollutants (POPs). Our aim in the present study was to compare serum xenoandrogenic activity between study groups with different POP exposures and to evaluate correlations to the POP proxy markers 2,2′,4,4′,5,5′-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p′-DDE).
Methods
We determined xenoandrogenic activity in the serum fraction containing the lipophilic POPs but free of endogenous hormones. Adult male serum (n = 261) from Greenland, Sweden, Warsaw (Poland), and Kharkiv (Ukraine) was analyzed. Xenoandrogenic activity was determined as the effect of serum extract alone (XAR) and in the presence of the synthetic AR agonist R1881 (XARcomp) on AR transactivated luciferase activity.
Results
The study groups differed significantly with respect to XARcomp activity, which was increased in the Inuits and decreased in the European study groups; we observed no difference for XAR activity. We found the highest level of the AR antagonist p,p′-DDE in Kharkiv, and accordingly, this study group showed the highest percent of serum samples with decreased XARcomp activities. Furthermore, the percentage of serum samples with decreased XARcomp activities followed the p,p′-DDE serum level for the European study groups. No correlations between serum XAR or XARcomp activities and the two POP markers were revealed.
Conclusions
The differences in XARcomp serum activity between the study groups suggest differences in chemical exposure profiles, genetics, and/or lifestyle factors.
doi:10.1289/ehp.9353
PMCID: PMC2174397  PMID: 18174946
AR activity; CB-153; human serum; polychlorinated biphenyls; p,p′-DDE
15.  Dietary exposure to methyl mercury and PCB and the associations with semen parameters among Swedish fishermen 
Environmental Health  2007;6:14.
Dietary POP exposure have shown negative effects on sperm motility and sperm chromatin integrity, as well as an increased proportion of Y-chromosome bearing sperms. However, it has been suggested that in epidemiological studies investigating persistent organochlorine pollutant (POP)-toxicity, other pollutants occurring simultaneously may carry an increased risk of effects, which may obscure a clear interpretation of the role of POP toxicity. One such pollutant is methyl mercury (MeHg), which has been found in fatty fish from the Baltic Sea and as a consequence men with a high consumption of such fish has been found to have twice the MeHg levels compared to men with a low fish consumption.
The aim of the present study was to assess if exposure to MeHg affects male reproductive function, assessed by measuring human sperm motility, sperm concentration, total sperm count, sperm chromatin integrity and the proportion of Y-chromosome bearing sperms. Secondly we also investigated a possible interaction between MeHg and 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl (CB-153), a biomarker for POP exposure, with respect to sperm outcome measures.
Blood and semen samples were collected from 195 Swedish fishermen with a mean age of 47 (range 24–67 years). Blood levels of MeHg ranged from 0.11 to 16.59 μg/L (median 2.25 μg/L) and serum levels of CB-153 from 37 to 1460 ng/g lipid (median 190 ng/g lipid).
The analyses revealed no association between MeHg and any of the outcomes investigated. Although men with low MeHg and high CB-153 had slightly higher DNA Fragmentation Index and fraction of Y-chromosome bearing sperms than men with low levels of both compounds, the effects were not statistically significant. In conclusion, we did not find any associations between MeHg exposure and semen quality or quantity in the dose range observed neither was any synergistic effects between MeHg and CB-153 noted.
doi:10.1186/1476-069X-6-14
PMCID: PMC1871583  PMID: 17488503
16.  Impact of PCB and p,p′-DDE Contaminants on Human Sperm Y:X Chromosome Ratio: Studies in Three European Populations and the Inuit Population in Greenland 
Environmental Health Perspectives  2005;114(5):718-724.
Objective
Recent studies indicate that persistent organohalogen pollutants (POPs) may contribute to sex ratio changes in offspring of exposed populations. Our aim in the present study was to investigate whether exposure to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153) and dichlorodiphenyldichloroethene (p,p′-DDE) affects sperm Y:X chromosome distribution.
Subjects and methods
We obtained semen and blood for analysis of PCB-153 and p,p′-DDE levels from 547 men from Sweden, Greenland, Poland (Warsaw), and Ukraine (Kharkiv), with regionally different levels of POP exposure. The proportion of Y- and X-chromosome–bearing sperm in the semen samples was determined by two-color fluorescence in situ hybridization analysis.
Results
Swedish and Greenlandic men had on average significantly higher proportions of Y sperm (in both cohorts, 51.2%) and correspondingly higher lipid-adjusted concentrations of PCB-153 (260 ng/g and 350 ng/g, respectively) compared with men from Warsaw (50.3% and 22 ng/g) and Kharkiv (50.7% and 54 ng/g). In the Swedish cohort, log-transformed PCB-153 and log-transformed p,p′-DDE variables were significantly positively associated with Y-chromosome fractions (p-values 0.04 and < 0.001, respectively). On the contrary, in the Polish cohort PCB-153 correlated negatively with the proportion of Y-bearing fraction of spermatozoa (p = 0.008).
Conclusions
The present study indicates that POP exposure might be involved in changing the proportion of ejaculated Y-bearing spermatozoa in human populations. Intercountry differences, with different exposure situations and doses, may contribute to varying Y:X chromosome ratios.
doi:10.1289/ehp.8668
PMCID: PMC1459925  PMID: 16675426
polychlorinated biphenyls; POP; p, p′-DDE; sex chromosomes; sex ratio; sperm
17.  Inter-population variations in concentrations, determinants of and correlations between 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE): a cross-sectional study of 3161 men and women from Inuit and European populations 
Environmental Health  2005;4:27.
Background
The study is part of a collaborative project (Inuendo), aiming to assess the impact of dietary persistent organochlorine pollutants (POPs) on human fertility. The aims with the present study are to analyze inter-population variations in serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE), to assess inter-population variations in biomarker correlations, and to evaluate the relative impact of different determinants for the inter-individual variations in POP-biomarkers.
Method
In study populations of 3161 adults, comprising Greenlandic Inuits, Swedish fishermen and their wives, and inhabitants from Warsaw, Poland and Kharkiv, Ukraine, serum concentrations of CB-153 and p,p'-DDE, were analysed by gas chromatography-mass spectrometry.
Results
The median serum concentrations of CB-153 were for male and female Inuits 200 and 110, for Swedish fishermen 190 and their wives 84, for Kharkiv men and women 44 and 27, and for Warsaw men and women 17 and 11 ng/g lipids, respectively. The median serum concentrations of p,p'-DDE were for Kharkiv men and women 930 and 650, for male and female Inuits 560 and 300, for Warsaw men and women 530 and 380, and for Swedish fishermen 240 and their wives 140 ng/g lipids, respectively. The correlation coefficients between CB-153 and p,p'-DDE varied between 0.19 and 0.92, with the highest correlation among Inuits and the lowest among men from Warsaw. Men had averagely higher serum concentrations of CB-153 and p,p'-DDE, and there were positive associations between age and the POP-biomarkers, whereas the associations with BMI and smoking were inconsistent. Dietary seafood was of importance only in the Inuit and Swedish populations.
Conclusion
CB-153 concentrations were much higher in Inuits and Swedish fishermen's populations than in the populations from Eastern Europe, whereas the pattern was different for p,p'-DDE showing highest concentrations in the Kharkiv population. The correlations between the POP-biomarkers varied considerably between the populations, underlining that exposure sources differ and that the choice of representative biomarkers of overall POP exposure has to be based on an analysis of the specific exposure situation for each population. Age and gender were consistent determinants of serum POPs; seafood was of importance only in the Inuit and Swedish populations.
doi:10.1186/1476-069X-4-27
PMCID: PMC1308838  PMID: 16283941
18.  Serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in relation to markers of reproductive function in young males from the general Swedish population. 
Environmental Health Perspectives  2003;111(4):409-413.
A time-related deterioration in male reproductive function caused by exposure to endocrine disrupters, including persistent organochlorines (POCs), has been hypothesized. In animal studies, POCs were found to have adverse effects on male reproductive function. However, little is known about the impact of POC exposure on reproductive parameters in men. In a study of 305 young Swedish men 18-21 years old from the general population, we correlated lipid-adjusted serum levels of 2,2',4,4',5,5' -hexachlorobiphenyl (CB-153)--an index substance for POC exposure--to markers of male reproductive function: testis size assessed by ultrasound, sperm concentration, total sperm count, sperm motility assessed manually and with a computer-aided sperm analyzer (CASA), and serum levels of follicle-stimulating hormone, inhibin B, testosterone, sexual hormone-binding globulin (SHBG), luteinizing hormone, and estradiol. We found weak but statistically significant, negative correlations between CB-153 levels and both the testosterone:SHBG ratio (r = -0.25, p < 0.001)--a measure of the biologically active free testosterone fraction--and CASA sperm motility (r = -0.13, p = 0.02). No statistically significant association with other seminal, hormonal, or clinical markers of male reproductive function was found. In previous studies of more highly POC-exposed groups of adult men, the correlation between POC exposure, including CB-153, and free testosterone levels was not statistically significant. The present study gives some tentative support for weak negative effects of CB-153 exposure on sperm motility and free testosterone levels in young men, but further semen studies on more highly exposed groups may give more firm conclusions on the hazard for male reproductive function from dietary POC exposure.
PMCID: PMC1241420  PMID: 12676591

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