Maternal smoking during pregnancy and daughters' risk of gestational diabetes and obesity.

AIMS/HYPOTHESIS: The primary aim of the study was to investigate the risk of developing gestational diabetes in women who were exposed to tobacco smoke in utero. Secondary aims were to assess the risk of obesity and non-gestational diabetes. METHODS: Data were retrieved from the Medical Birth Register of Sweden for women who were born in 1982 (when smoking data were first registered) or later and who had given birth to at least one child; 80,189 pregnancies were included. The associations between in utero smoking exposure (three categories: non-smokers, 1-9 cigarettes/day [moderately exposed] and >9 cigarettes/day [heavily exposed]) and subsequent gestational diabetes (n = 291), non-gestational diabetes (n = 280) and obesity (n = 7,300) were assessed. RESULTS: The adjusted ORs (aORs) of gestational diabetes were increased among women who were moderately (1.62, 95% CI 1.24, 2.13) and heavily (1.52, 95% CI 1.12, 2.06) exposed. The corresponding aORs of obesity were 1.36 (95% CI 1.28, 1.44) and 1.58 (95% CI 1.48, 1.68), respectively. A reduced OR for non-gestational diabetes was seen in the offspring of heavy smokers (aOR 0.66, 95% CI 0.45, 0.96). CONCLUSIONS/INTERPRETATION: Women exposed to smoking during fetal life were at higher risk of developing gestational diabetes and obesity.

Polybrominated diphenyl ethers in maternal serum, umbilical cord serum, colostrum and mature breast milk. Insights from a pilot study and the literature.

Human serum and mother's milk are frequently used to assess exposure to polybrominated diphenyl ethers (PBDEs), including transplacental transfer to the foetus. However, little is known about the kinetics of PBDEs, especially the highly brominated BDE congeners. In this pilot study, maternal serum samples were collected from 10 women at delivery and five to six weeks post partum. Umbilical serum was also obtained. Milk was donated two to five days, and five to six weeks after delivery. The amount of PBDEs in these samples was determined using liquid-liquid extraction and GC/MS. Low, moderately and highly brominated diphenyl ethers were present in umbilical cord serum, indicating placental transfer. The lipid-adjusted levels of BDE-47, BDE-207 and BDE-209 were similar in maternal and umbilical cord serum, whereas the cord serum levels for the penta- to octa-BDEs quantified were lower than in maternal serum. Marked changes were seen in the congener pattern in breast milk during the first month of lactation, whereas maternal serum levels did not change significantly. The general pattern was an enrichment of low to moderately brominated congeners (i.e. from BDE-17 to BDE-154, with the exception of BDE-28) in colostrum compared with maternal serum. In contrast, more highly brominated congeners were found at similar, or lower levels in colostrum than in maternal serum. After the transition from colostrum to mature milk, the levels of BDE-153 and BDE-209 were substantially reduced, and BDE-209 was below the limit of detection in 6 out of 9 samples. A literature review on the design and reporting of studies on the transfer of PBDEs from mother to infant revealed a lack of transparency in many cases. The use of the recently published STROBE-ME guidelines is therefore recommended.

No secular trend over the last decade in sperm counts among Swedish men from the general population.

INTRODUCTION: Based on historical data, a decline in sperm counts during the years 1940-1990 has been suggested and aetiologically linked to a concomitant increase in the incidence of testicular cancer. This study, focusing on possible changes in sperm parameters among young Swedish men, during the past 10 years, was specifically designed in order to answer the question of whether there is a continuing decline in sperm counts. METHODS: During the period 2008-2010, 295 young (17-20 years; median 18) men born and raised in Sweden were recruited at the age they were supposed to undergo medical examination prior to military service. The participants filled in questionnaires, underwent andrological examination and delivered an ejaculate. Their semen parameters were compared with those of a similar cohort of men (n = 216) recruited in the year 2000-2001. RESULTS: No significant changes (means; 2000-2001 versus 2008-2010) in sperm concentration (78 × 106/ml versus 82 × 106/ml; P = 0.54), semen volume (3.1 ml versus 3.0 ml; P = 0.26) or total sperm counts (220 × 106 versus 250 × 106; P = 0.18) were found. The proportion of progressively motile spermatozoa also remained unchanged. CONCLUSIONS: Between the years 2000 and 2010 we found no evidence of time-related deterioration of semen parameters among young Swedish men from the general population. This finding does not exclude that such a decrease may have taken place before year 2000. If the risk of testicular cancer is linked to the sperm counts, the increase in incidence of this malignancy should be levelling off in southern Sweden in the next 10-15 years.

Exposure to cadmium and persistent organochlorine pollutants and its association with bone mineral density and markers of bone metabolism on postmenopausal women.

Environmental contaminants such as cadmium and persistent organochlorine pollutants have been proposed as risk factors of osteoporosis, and women may be at an increased risk. To assess associations between exposure to cadmium and two different POPs (2,2',4,4',5,5'-hexachlorobiphenyl CB-153, 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene p,p'-DDE), on one hand, and bone effects, on the other, in a population-based study among postmenopausal (60-70 years) Swedish women with biobanked blood samples. The study included 908 women and was designed to have a large contrast of bone mineral densities, measured with a single photon absorptiometry technique in the non-dominant forearm. Biochemical markers related to bone metabolism were analyzed in serum. Exposure assessment was based on cadmium concentrations in erythrocytes and serum concentrations of CB-153 and p,p'-DDE. Cadmium was negatively associated with bone mineral density and parathyroid hormone, positively with the marker of bone resorption. However, this association disappeared after adjustment for smoking. The major DDT metabolite (p,p'-DDE) was positively associated with bone mineral density, an association which remained after adjustment for confounders, but the effect was weak. There was no evidence that the estrogenic congener (CB-153) was associated with any of the bone markers. In conclusion, no convincing associations were observed between cadmium and POPs, on one hand, and bone metabolism markers and BMD, on the other.

Modifying effect of the AR gene trinucleotide repeats and SNPs in the AHR and AHRR genes on the association between persistent organohalogen pollutant exposure and human sperm Y:X ratio.

Persistent organohalogen pollutants (POPs) have been suggested to be involved in changing the proportion of ejaculated Y-bearing sperm. The androgen receptor (AR), aryl hydrocarbon receptor (AHR) and aryl hydrocarbon receptor repressor (AHRR) may modulate the effect of POPs with regard to previously observed sperm Y:X ratio changes. The objective of this study was to investigate whether sperm Y:X ratio changes in subjects exposed to 2,2'4,4'5,5'-hexachlorobiphenyl (CB-153) and dichlorodiphenyl dichloroethene (p,p'-DDE) were modified by polymorphisms in the AR, AHR and AHRR genes. Semen for analysis of Y- and X-bearing sperm by two-colour fluorescence in situ hybridization and blood for leukocyte DNA genotyping and analysis of CB-153 and p,p'-DDE concentrations were obtained from 195 Swedish fishermen. The polymorphic CAG and GGN repeats in the AR and the R554K and P185A single-nucleotide polymorphisms in the AHR and AHRR genes, respectively, were determined by direct sequencing and allele-specific PCR. The effect of p,p'-DDE was modified by CAG or GGN repeat category in relation to the proportion of Y-bearing sperm (P = 0.005 and 0.02 for CAG and GGN, respectively). Moreover, p,p'-DDE, but not CB-153, levels were associated with Y-sperm proportion in men with CAG < 22 (P < 0.001), but not in those carrying CAG > or = 22 (P = 0.73). This association was even more pronounced in subjects carrying a short CAG repeat in combination with an AHRR G-allele. The association in regard to p,p'-DDE was found for GGN = 23 but not for the GGN < 23 or GGN > 23 subgroups (P = 0.01, 0.44 and 0.99, respectively). In conclusion The endocrine-disrupting action of POPs, in relation to the observed changes in sperm Y:X ratio, may be modulated by the genes involved in sex steroid and dioxin-mediated pathways.

Relationships between sperm DNA fragmentation, sperm apoptotic markers and serum levels of CB-153 and p,p'-DDE in European and Inuit populations.

Persistent organochlorine pollutants (POPs) are suspected to interfere with hormone activity and the normal homeostasis of spermatogenesis. We investigated the relationships between sperm DNA fragmentation, apoptotic markers identified on ejaculated spermatozoa and POP levels in the blood of 652 adult males (200 Inuits from Greenland, 166 Swedish, 134 Polish and 152 Ukrainian). Serum levels of 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl (CB-153), as a proxy of the total POP burden, and of 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE), as a proxy of the total DDT exposure were determined. Sperm DNA fragmentation was measured by using the TUNEL assay, whereas immunofluorescence methods were utilized for detecting pro-apoptotic (Fas) and anti-apoptotic (Bcl-xL) markers. Both TUNEL assay and apoptotic markers were statistically differed across the four populations. No correlation between neither sperm DNA fragmentation nor apoptotic sperm parameters and the large variations in POPs exposure was observed for the separate study groups. However, considering the European populations taken together, we showed that both %TUNEL positivity and Bcl-xL were related to CB-153 serum levels, whereas our study failed to demonstrate any relations between DDE and %TUNEL positivity and apoptotic sperm biomarkers (Fas and Bcl-xL) in any region or overall regions. These results suggest that CB-153 and related chemicals might alter sperm DNA integrity and Bcl-xL levels in European adult males, but not in the highly exposed Inuit men. Additional issues (genetic background, lifestyle habits and characterization of total xeno-hormonal activities) need to be investigated in order to fully assess the population variations observed.

Time to pregnancy as a function of male and female 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).

BACKGROUND: Persistent organochlorine pollutants (POP) may affect both the female and male reproductive system in animals as well as in humans. METHODS: Blood samples were collected from pregnant women and their partners from Greenland, Warsaw and Kharkiv, and from a cohort of Swedish fishermen's wives. Blood samples were analysed for 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE). Information on the participants' fertility, measured as time to pregnancy (TTP), was collected. In total, 778 men and 1505 women were included in the analyses. RESULTS: The data from Warsaw, Kharkiv and the Swedish fishermen's wives indicated no effect of either male or female exposure to POP on TTP. However, among men and women from Greenland, there seemed to be an association between serum concentrations of CB-153 and p,p'-DDE and prolonged TTP. Due to the strong intra-individual correlation between CB-153 and p,p'-DDE in the Greenlandic population, it was not possible to determine whether the risk was associated with CB-153 or p, p'-DDE or was an interaction between the two compounds. CONCLUSIONS: The overall results of the present study create a somewhat ambiguous pattern, but give some support to the idea that dietary POP exposure might be harmful for couple fertility.

Exposure to PCB and p, p'-DDE in European and Inuit populations: impact on human sperm chromatin integrity.

BACKGROUND: Persistent organochlorine pollutants (POP), such as polychlorinated biphenyls (PCB) and dichlorodiphenyldichloroethylene (p, p'-DDE), are widely found in the environment and considered potential endocrine-disrupting compounds (EDC). Their impact on male fertility is still unknown. METHODS: To explore the hypothesis that POP is associated with altered sperm chromatin integrity, a cross-sectional study involving 707 adult males (193 Inuits from Greenland, 178 Swedish fishermen, 141 men from Warsaw, Poland, and 195 men from Kharkiv, Ukraine) was carried out. Serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), as a proxy of the total PCB burden, and of p,p'-DDE were determined. Sperm chromatin structure assay (SCSA) was used to assess sperm DNA/chromatin integrity. RESULTS: We found a strong and monotonically increasing DNA fragmentation index with increasing serum levels of CB-153 among European but not Inuit men, reaching a 60% higher average level in the highest exposure group. No significant associations were found between SCSA-derived parameters and p, p'-DDE serum concentrations. CONCLUSION: These results suggest that human dietary PCB exposure might have a negative impact on the sperm chromatin integrity of adult males but additional issues, including differences in the genetic background and lifestyle habits, still need to be elucidated.

Exposure to persistent organochlorine pollutants and seminal levels of markers of epididymal and accessory sex gland functions in Swedish men.

BACKGROUND: A major exposure route for persistent organochlorine pollutants (POPs) in Sweden is through consumption of fatty fish from the Baltic Sea. Endocrine disruptors, such as POPs, may have a negative impact on sperm quality. The present study aimed to investigate whether exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) affects epididymal and accessory sex gland function. METHODS: 157 fishermen from the coastal stretches of Sweden, aged 27-67 years, provided semen samples which were analyzed for prostate-specific antigen (PSA), neutral alpha-glucosidase (NAG), fructose and zinc levels. Serum levels of CB-153 and p'p-DDE were determined. RESULTS: The median CB-153 serum level was 189 ng/g lipid (range 40-1460) and a median p,p'-DDE serum level 231 ng/g lipid (range 40-2252). There was a significant linear association between CB-153 and total amount of PSA (slope [beta] = -2.5, 95% confidence interval [CI] -4.0, -0.9; P = 0.02). With age, abstinence time and smoking included in the model the association became non-significant (beta = -1.4, 95% CI-3.0, 0.1; P = 0.07). There were no significant associations between CB-153 and zinc, fructose and NAG. As for the exposure variable p,p'-DDE and the outcome variables, no significant associations were found. CONCLUSIONS: The study gives only very limited support of an association between CB-153 in serum and total PSA, and a random finding cannot be excluded.

Exposure to CB-153 and p,p'-DDE and male reproductive function.

BACKGROUND: During the last decades, there has been concern that exposure to endocrine disruptors, such as persistent organochlorine pollutants (POPs), may contribute to an impairment of male reproductive function. To investigate whether exposure to 2,2'4,4'5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) affects semen quantity and quality and reproductive hormones, 195 Swedish fishermen, aged 24-65 years, were investigated. METHODS: The men provided semen samples which were analysed in a mobile laboratory unit. Blood samples and information relating to lifestyle, medical and reproductive history were obtained. RESULTS: The subjects had a median CB-153 serum level of 193 ng/g lipid (range 39-1460) and a median p,p'-DDE serum level of 240 ng/g lipid (range 334-2251). When CB-153 was categorized into quintiles, the subjects in the quintile with the highest concentration (> 328 ng/g lipid), tended to have decreased sperm motility compared with the subjects in the lowest quintile (< 113 ng/g lipid). The age-adjusted mean difference was 9.9% (95% confidence interval -1.0 to 21% P = 0.08). We found no significant associations between p,p'-DDE and semen characteristics or reproductive hormones. CONCLUSION: The association between CB-153 and sperm motility, although not formally significant, is of interest considering the possible endocrine-disrupting effects of polychlorinated biphenyls (PCBs).