Association of in utero exposure to maternal smoking with reduced semen quality and testis size in adulthood: a cross-sectional study of 1,770 young men from the general population in five European countries.
Between 1996 and 1999, the authors invited all young men from five European countries who were undergoing compulsory medical examination for possible military service to participate in a study on male reproductive health. The participation rate was 19% in two cities in Denmark (n = 889), 17% in Oslo, Norway (n = 221), 13% in Turku, Finland (n = 313), 14% in Kaunas, Lithuania (n = 157), and 19% in Tartu, Estonia (n = 190). Each man provided a semen sample, was examined by a physician, and, in collaboration with his mother, completed a questionnaire about general and reproductive health, current smoking habits, and exposure to smoking in utero. After adjustment for confounding factors, men exposed to smoking in utero had a reduction in sperm concentration of 20.1% (95% confidence interval (CI): 6.8, 33.5) and a reduction in total sperm count of 24.5% (95% CI: 9.5, 39.5) in comparison with unexposed men. Percentages of motile and morphologically normal sperm cells were 1.85 (95% CI: 0.46, 3.23) and 0.64 (95% CI: -0.02, 1.30) percentage points lower, respectively, among men exposed in utero, and exposed men had a 1.15-ml (95% CI: 0.66, 1.64) smaller testis size. The associations were present when data from the study centers were analyzed separately (though not in Lithuania, where only 1% of mothers smoked during pregnancy), although the strength of the association varied. Maternal smoking may have long-term implications for the reproductive health of the offspring. This is another good reason to advise pregnant women to avoid smoking.
Arctic is contaminated with persistent organochlorine pollutants (POPs), and exposure to these compounds may differ between south and north in Norway. POPs may have negative impact on male reproductive characteristics. We compared serum levels of the CB-153 and p,p'-DDE in men who were born and had lived most of their lifetime south and north (close to or above the Arctic Circle) in Norway. We found no geographical differences in levels of CB-153 (south: 50 ng/g lipid (mean), north: 59 ng/g lipid; p=0.27) or sperm parameters. However, the levels of p,p'-DDE were higher in south than in north (81 ng/g lipid (mean) vs. 66 ng/g lipid; p=0.02), as were the levels of total and free testosterone. The FSH levels were lowest in south. A strong relationship between the CB-153 and the SHBG levels was observed. The regional differences observed for p,p'-DDE, testosterone and FSH were not reflected in the semen quality.
Since registration started in the 1950s, the incidence of testicular cancer (TC) in the Western world has increased, which is also the case in Norway. Men born in Norway during World War II (WWII), however, have a lower TC incidence than men born in the years before or after WWII. Increased fetal exposure to estrogen during the first trimester of pregnancy has been proposed as a risk factor for the development of TC later in life. Increased maternal weight is associated with higher insulin levels, leading to lower sex hormone-binding globulin levels and thereby increased levels of bioavailable estrogens for transplacental transfer from mother to fetus. The aim of the present study was therefore to examine whether there was an association between maternal weight and the incidence of TC among those who were born in a time period where the nutritional conditions changed, i.e., around the time of WWII. We compared data for a random sample of women giving birth in Oslo, Norway, in the years 1931 to 1955 with the TC incidence among men born in the whole country in the same time period. Maternal weight at delivery was used as a proxy for first-trimester weight. We found a correlation (Spearman's rho = 1.00, p
Seasonal, daylight-dependent variation in human spermatozoa counts, with lowest values during summer, has been suggested. To test this hypothesis, we performed a longitudinal study of semen quality and reproductive hormone levels in Norwegian men living north and south of the Arctic Circle. An ejaculate and a serum specimen were obtained both in summer and in winter from 92 volunteers in Tromsoe (69 degrees north latitude) and 112 in Oslo (60 degrees north latitude). Semen analyses were performed, and serum was assayed for FSH and inhibin B. The median spermatozoa concentration in Tromsoe after adjustment for abstinence period length was 49 x 10(6)/ml in summer and 54 x 10(6)/ml in winter. Corresponding values for Oslo were 59 x 10(6)/ml and 54 x 10(6)/ml. The seasonal differences in spermatozoa concentration were not statistically significant, nor were significant differences observed in median total spermatozoa count, semen volume, percentage progressive motile spermatozoa, or FSH. In Tromsoe, but not Oslo, inhibin B concentration was slightly, but significantly (P = 0.02) higher in winter than summer (229 ng/liter vs. 223 ng/liter). The length of the daylight period may have a slight impact on hormonal markers of spermatogenesis but does not cause substantial changes in spermatozoa numbers and motility.
It has been proposed that hypospadias, cryptorchidism and testicular cancer, as well as decreasing sperm quality are symptoms of an underlying entity called testicular dysgenesis syndrome (TDS). We wanted to study the risk factors for hypospadias and compare them with those of the other conditions belonging to TDS. A large case-control study was undertaken on data on all live-born boys registered in the Medical Birth Registry of Norway during the period 1967-1998 (n = 961 396; hypospadias cases = 2382). Logistic regression analysis was used to study the association between potential risk factors and hypospadias, estimated by odds ratio (OR). The risk factors for hypospadias were divided into four categories: (i) maternal characteristics, e.g. low parity [p(trend)
Comment In: Int J Androl. 2004 Aug;27(4):189-9115271197
A high sperm DNA fragmentation index (DFI) is associated with reduced fertility. DFI is influenced by the balance between reactive oxygen species and antioxidants. A circannual variation in melatonin, an antioxidant and free radical scavenger, could thus impact semen quality and fertility. The association between the major melatonin metabolite, urine 6-sulfatoxymelatonin (aMT6s), and DFI was analyzed in 110 Oslo men (south of the Arctic Circle) and 86? Tromsoe men (north of the Arctic Circle). Two semen analyses, summer and winter, and four urine samples (early/late summer; early/late winter), were analyzed. The associations between aMT6s in urine and DFI were characterized in a cross-sectional and longitudinal manner using correlation analysis and linear regression. Regardless of season and location, no significant correlations between aMT6s and DFI were observed. The correlation coefficients for associations between changes over time (early winter-early summer) in aMT6s and DFI were for the total cohort: rho = -0.08 (P = 0.322), for the Oslo cohort: rho = -0.07 (P = 0.485), and for the Tromsoe cohort: rho = -0.14 (P = 0.273), respectively. Similar results were seen when comparing late winter and late summer. There was no any statistically significant correlation between changes over time in aMT6s and DFI for men with DFI below and above the median value (10%), respectively. The seasonal variation in melatonin excretion seems not to have any impact on DFI.
Genome-wide association (GWA) studies have reported 19 distinct susceptibility loci for testicular germ cell tumor (TGCT). A GWA study for TGCT was performed by genotyping 610 240 single-nucleotide polymorphisms (SNPs) in 1326 cases and 6687 controls from Sweden and Norway. No novel genome-wide significant associations were observed in this discovery stage. We put forward 27 SNPs from 15 novel regions and 12 SNPs previously reported, for replication in 710 case-parent triads and 289 cases and 290 controls. Predefined biological pathways and processes, in addition to a custom-built sex-determination gene set, were subject to enrichment analyses using Meta-Analysis Gene Set Enrichment of Variant Associations (M) and Improved Gene Set Enrichment Analysis for Genome-wide Association Study (I). In the combined meta-analysis, we observed genome-wide significant association for rs7501939 on chromosome 17q12 (OR = 0.78, 95% CI = 0.72-0.84, P = 1.1 ? 10(-9)) and rs2195987 on chromosome 19p12 (OR = 0.76, 95% CI: 0.69-0.84, P = 3.2 ? 10(-8)). The marker rs7501939 on chromosome 17q12 is located in an intron of the HNF1B gene, encoding a member of the homeodomain-containing superfamily of transcription factors. The sex-determination gene set (false discovery rate, FDRM