Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs.

Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs)1, which influences offspring development and adult phenotypes1-7. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood8. Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs (mt-tRNAs) and their fragments (mt-tsRNAs) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with body mass index, and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction. Single-embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilization and suggested their involvement in the control of early-embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.

An update on semen quality among young Finnish men and comparison with Danish data.

BACKGROUND: Finnish men used to have higher semen quality than Danish men. However, recent studies showed that semen quality in Finland has declined, but it has been relatively stable in Denmark. OBJECTIVE: This study aimed to compare new data on semen quality of the young Finnish men to that of Danish men. MATERIALS AND METHODS: In this cross-sectional study, 18- to 19-year-old men residing in Turku, Finland and Copenhagen, Denmark, were invited to participate in 2008-2011. Each man filled in a questionnaire, provided one semen sample and underwent andrological examination. Semen samples were analyzed according to WHO. Multiway ANOVA was used to adjust semen variables for duration of sexual abstinence and age (and time from ejaculation to the start of semen analysis for sperm motility). RESULTS: Altogether 287 Finnish men and 873 Danish men participated in the study. The adjusted median sperm concentrations were 49 and 47 million/mL for Finnish and Danish men, respectively (p = 0.48). The adjusted median total sperm counts were 148 million in Finland and 146 million in Denmark (p = 0.87). The adjusted median percentages of morphologically normal spermatozoa were 6.9% in Finland and 6.5% in Denmark, p = 0.27. Finnish men had higher adjusted median percentages of motile spermatozoa (A+B+C) than Danish men (80% vs. 69%, p < 0.001). The proportion of men who had low semen quality (sperm concentration, percentage of morphologically normal spermatozoa or percentage of progressively motile spermatozoa below WHO reference limits) was lower in Finland (25.4%) than in Denmark (34.6%), p = 0.004. DISCUSSION: Considerable percentage of men in both countries had low semen quality. The deteriorating semen quality in Finland may result in decreasing fecundity, which is a cause of concern. CONCLUSION: The formerly high semen quality in Finland has converged to the lower Danish levels. Our findings demonstrate the importance of continuing surveillance of semen quality.

Country-specific chemical signatures of persistent organic pollutants (POPs) in breast milk of French, Danish and Finnish women.

The present study compares concentrations and chemical profiles of an extended range of persistent organic pollutants (dioxins, polychlorobiphenyls, brominated flame retardants and organochlorine pesticides) in breast milk samples from French (n = 96), Danish (n = 438) and Finnish (n = 22) women. Median exposure levels observed in French women (WHO-TEQ2005 PCDD/F = 6.1 pg/g l.w., WHO-TEQ2005 dl-PCB = 4.3 pg/g l.w., sum of 6 ndl-PCB = 85.2 ng/g l.w., sum of 7 i-PBDE = 1.5 ng/g l.w.) appeared overall lower than in Danish and Finnish women for all examined POPs, except for α-HBCD (2-fold higher level at 0.6 ng/g l.w.). Furthermore, the observed exposure levels of dioxins and PCBs were higher in Danish women (WHO-TEQ2005 PCDD/F = 13.2 pg/g l.w., WHO-TEQ2005 dl-PCB = 6.6 pg/g l.w., sum of 6 ndl-PCB = 162.8 ng/g l.w.) compared to Finnish women (WHO-TEQ2005 PCDD/F = 9.0 pg/g l.w., WHO-TEQ2005 dl-PCB = 4.6 pg/g l.w., sum of 6 ndl-PCB = 104.0 ng/g l.w.), whereas the concentrations of PBDEs were similar for Danish and Finnish women (sum of 7 i-PBDE = 4.9 and 5.2 ng/g l.w. respectively). The organochlorine (OC) pesticide contamination profile, determined in a subset of French samples, was dominated by p,p'-DDE (56.6%), followed by ß-HCH (14.2%), HCB (9.7%) and dieldrin (5.2%), while other compounds were only minor contributors (<5%). The three countries appeared to be discriminated by the observed contamination patterns of the PCDD/F versus PCB, and the 1,2,3,6,7,8-HxCDD versus 1,2,3,4,7,8-HxCDD ratios, in addition to the relative contributions of specific congeners to the contamination profile (PCBs #118 and #156, PBDEs #28, #47, #99 and #153). In conclusion, unique chemical signatures were observed for each country on the basis of some POP congeners. Future biomonitoring studies will need to consider the high variability of individual exposure profiles in relation to multiple exposure sources but also physiological and metabolic differences.

Compensated reduction in Leydig cell function is associated with lower semen quality variables: a study of 8182 European young men.

STUDY QUESTION: Is the Leydig cell function of young European men associated with semen quality? SUMMARY ANSWER: Compensated reduction in Leydig cell function, defined as increased LH concentration combined with adequate testosterone production is associated with lower semen quality. WHAT IS ALREADY KNOWN: Semen quality of young European men shows a heterogeneous pattern. Many have sperm counts below and in the lower WHO reference where there nevertheless is a significant risk of subfecundity. Little is known about differences in Leydig cell function between men with semen quality below and within the WHO reference range. STUDY DESIGN, SIZE AND DURATION: A coordinated, cross-sectional population-based study of 8182 men undertaken in 1996-2010. PARTICIPANTS, SETTING AND METHOD: Young men (median age 19.1 years) were investigated in centres in Denmark, Estonia, Finland, Germany Latvia, Lithuania, and Spain. The men originated from the general populations, all were young, almost all were unaware of their fecundity and each provided a semen and blood sample. Associations between semen parameters and serum levels of testosterone and luteinising hormone (LH), calculated free testosterone, and ratios between serum testosterone and LH were determined. MAIN RESULT AND ROLE OF CHANCE: Serum testosterone levels were not associated with sperm concentrations, total sperm counts, or percentage of motile or morphologically normal spermatozoa. There was an inverse association between the semen parameters and serum LH levels, and accordingly a positive association to testosterone/LH ratio and calculated-free-testosterone/LH ratio. LIMITATIONS, REASON FOR CAUTION: The size of the study mitigates the intra-individual variability concern. The distinction between different sub-categories of sperm motility and sperm morphology is subjective despite training. However, inter-observer variation would tend towards non-differential misclassification and would decrease the likelihood of detecting associations between reproductive hormone levels and semen variables, suggesting that the presented associations might in reality be even stronger than shown. Although we adjusted for confounders, we cannot of course exclude that our results can be skewed by selection bias or residual confounding. WIDER IMPLICATIONS OF THE FINDINGS: Compensated reduction in Leydig cell function, defined as increased LH concentration combined with adequate testosterone production is associated with lower semen quality. This is apparent even within the WHO reference range of semen quality. It is unknown whether impaired Leydig cell function in young men may confer an increased risk of acquired testosterone deficiency later in life. STUDY FUNDING/COMPETING INTERESTS: Support from The Research Fund of Rigshospitalet (grant no. R42-A1326) to N.J. made this study possible. The background studies of young men have been supported economically by several grants. ITALIC! Denmark: The European Union (contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603 and most recently FP7/2007-2013, DEER Grant agreement no. 212844), The Danish Research Council (grants nos. 9700833 2107-05-0006), The Danish Agency for Science, Technology and Innovation (Grant no. 271070678), Rigshospitalet (Grant no. 961506336), The University of Copenhagen (Grant no. 211-0357/07-3012), The Danish Ministry of Health and the Danish Environmental Protection Agency, A.P. Møller and wife Chastine McKinney Møllers foundation, and Svend Andersens Foundation. ITALIC! Finland: European Union (contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT- 2002-00603 and most recently FP7/2008-2012, DEER Grant agreement no. 212844), The Academy of Finland, Turku University Hospital Funds, Sigrid Juselius Foundation. ITALIC! Estonia, Latvia and Lithuania: European Union (QLRT-2001-02911), the Estonian Science Foundation, grant number 2991, Lithuanian Foundation for Research, Organon Agencies B.V. and the Danish Research Council, grant no. 9700833. ITALIC! Germany: European Union (contract numbers QLK4-CT-2002-00603). ITALIC! Spain: European Commission QLK4-1999-01422. M.F. received support from the Spanish Ministry of Science and Innovation (Program Ramon y Cajal). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. None of the authors have any competing interests to declare.

Association between chemical pattern in breast milk and congenital cryptorchidism: modelling of complex human exposures.

During the past four decades, there has been an increase in the incidence rate of male reproductive disorders in some, but not all, Western countries. The observed increase in the prevalence of male reproductive disorders is suspected to be ascribable to environmental factors as the increase has been too rapid to be explained by genetics alone. To study the association between complex chemical exposures of humans and congenital cryptorchidism, the most common malformation of the male genitalia, we measured 121 environmental chemicals with suspected or known endocrine disrupting properties in 130 breast milk samples from Danish and Finnish mothers. Half the newborns were healthy controls, whereas the other half was boys with congenital cryptorchidism. The measured chemicals included polychlorinated biphenyls (PCBs), polybrominated diphenyl-ethers, dioxins (OCDD/PCDFs), phthalates, polybrominated biphenyls and organochlorine pesticides. Computational analysis of the data was performed using logistic regression and three multivariate machine learning classifiers. Furthermore, we performed systems biology analysis to explore the chemical influence on a molecular level. After correction for multiple testing, exposure to nine chemicals was significantly different between the cases and controls in the Danish cohort, but not in the Finnish cohort. The multivariate analysis indicated that Danish samples exhibited a stronger correlation between chemical exposure patterns in breast milk and cryptorchidism than Finnish samples. Moreover, PCBs were indicated as having a protective effect within the Danish cohort, which was supported by molecular data recovered through systems biology. Our results lend further support to the hypothesis that the mixture of environmental chemicals may contribute to observed adverse trends in male reproductive health.

Associations between congenital cryptorchidism in newborn boys and levels of dioxins and PCBs in placenta.

In animal studies, exposure to dioxins has been associated with disrupted development of the male reproductive system, including testicular maldescent. Some polychlorinated biphenyls (PCBs) have also dioxin-like effects. In addition, one previous case-control study has reported an association between congenital cryptorchidism and colostrum PCB levels. We performed a case-control study to evaluate whether congenital cryptorchidism in boys was associated with increased levels of dioxins or PCBs in placenta reflecting foetal exposure. In addition, associations between placenta levels of these chemicals and reproductive hormone levels in boys at 3 months were studied. Placentas were collected in a Danish-Finnish joint prospective cohort study on cryptorchidism (1997-2001). The boys were examined for cryptorchidism at birth and at 3 months. Altogether, 280 placentas [112 Finnish (56 cases, 56 controls) and 168 Danish (39 cases, 129 controls)] were analysed for 17 toxic polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and 37 PCBs (including 12 dioxin-like PCBs). Infant serum samples taken at 3 months were analysed for reproductive hormones. No significant differences between cases and controls were observed in either country in dioxin WHO-TEq levels (median 9.78 vs. 8.47 pg/g fat, respectively, in Finland, and 11.75 vs. 10.88 pg/g fat in Denmark) or PCB WHO-TEq levels (median 2.12 vs. 2.15 pg/g fat in Finland, 2.34 vs. 2.10 pg/g fat in Denmark) or total-TEq levels (median 11.66 vs. 10.58 pg/g fat in Finland, 13.94 vs. 13.00 pg/g fat in Denmark). Placenta WHO-TEq levels of dioxins were not associated with infant reproductive hormone levels at 3 months. In Finland, PCB WHO-TEq levels in placenta associated positively with infant LH levels. WHO-TEq levels of dioxins and PCBs and total-TEq levels were higher in Danish than Finnish samples. In conclusion, no association between placenta levels of dioxins or PCBs and congenital cryptorchidism was found. Significant country differences in chemical levels were observed.

Recent adverse trends in semen quality and testis cancer incidence among Finnish men.

Impaired semen quality and testicular cancer may be linked through a testicular dysgenesis syndrome of foetal origin. The incidence of testis cancer has been shown to increase among Finnish men, whereas there is no recent publication describing temporal trends in semen quality. Therefore, we carried out a prospective semen quality study and a registry study of testis cancer incidence among Finnish men to explore recent trends. A total of 858 men were investigated in the semen quality study during 1998-2006. Median sperm concentrations were 67 (95% CI 57-80) million/mL, 60 (51-71) and 48 (39-60) for birth cohorts 1979-81, 1982-83 and 1987; total sperm counts 227 (189-272) million, 202 (170-240) and 165 (132-207); total number of morphologically normal spermatozoa 18 (14-23) million, 15 (12-19) and 11 (8-15). Men aged 10-59 years at the time of diagnosis with testicular cancer during 1954-2008 were included in the registry study, which confirmed the increasing incidence of testicular cancer in recent cohorts. These simultaneous and rapidly occurring adverse trends suggest that the underlying causes are environmental and, as such, preventable. Our findings necessitate not only further surveillance of male reproductive health but also research to detect and remove the underlying factors.

Temperature changes associated with radiofrequency exposure near authentic metallic implants in the head phantom--a near field simulation study with 900, 1800 and 2450 MHz dipole.

Along with increased use of wireless communication devices operating in the radiofrequency (RF) range, concern has been raised about the related possible health risks. Among other concerns, the interaction of medical implants and RF devices has been studied in order to assure the safety of implant carriers under various exposure conditions. In the RF range, the main established quantitative effect of electromagnetic (EM) fields on biological tissues is heating due to vibrational movements of water molecules. The temperature changes induced in tissues also constitute the basis for the setting of RF exposure limits and recommendations. In this study, temperature changes induced by electromagnetic field enhancements near passive metallic implants have been simulated in the head region. Furthermore, the effect of the implant material on the induced temperature change was evaluated using clinically used metals with the highest and the lowest thermal conductivities. In some cases, remarkable increases in maximum temperatures of tissues (as much as 8 °C) were seen in the near field with 1 W power level whereas at lower power levels significant temperature increases were not observed.

Country-specific chemical signatures of persistent environmental compounds in breast milk.

Recent reports have confirmed a worldwide increasing trend of testicular cancer incidence, and a conspicuously high prevalence of this disease and other male reproductive disorders, including cryptorchidism and hypospadias, in Denmark. In contrast, Finland, a similarly industrialized Nordic country, exhibits much lower incidences of these disorders. The reasons behind the observed trends are unexplained, but environmental endocrine disrupting chemicals (EDCs) that affect foetal testis development are probably involved. Levels of persistent chemicals in breast milk can be considered a proxy for exposure of the foetus to such agents. Therefore, we undertook a comprehensive ecological study of 121 EDCs, including the persistent compounds dioxins, polychlorinated biphenyls (PCBs), pesticides and flame retardants, and non-persistent phthalates, in 68 breast milk samples from Denmark and Finland to compare exposure of mothers to this environmental mixture of EDCs. Using sophisticated, bioinformatic tools in our analysis, we reveal, for the first time, distinct country-specific chemical signatures of EDCs with Danes having generally higher exposure than Finns to persistent bioaccumulative chemicals, whereas there was no country-specific pattern with regard to the non-persistent phthalates. Importantly, EDC levels, including some dioxins, PCBs and some pesticides (hexachlorobenzene and dieldrin) were significantly higher in Denmark than in Finland. As these classes of EDCs have been implicated in testicular cancer or in adversely affecting development of the foetal testis in humans and animals, our findings reinforce the view that environmental exposure to EDCs may explain some of the temporal and between-country differences in incidence of male reproductive disorders.

Epidemiology and pathogenesis of cryptorchidism.

Prospective clinical studies have shown that the prevalence of cryptorchidism among boys with birth weight > or =2500 g has increased in UK from 2.7 to 4.1% between the 1950s and the 1980s and in Denmark from 1.8 to 8.4% between the 1950s and the 1990s. In similar studies performed in different countries during the last two decades the figures have varied from 2.1 to 8.4%. Due to spontaneous descent of the testes lower figures, i.e. between 0.9 and 1.8% have been described at 3 months. Acquired cryptorchidism contributes to the increase in the rate of cryptorchidism in school-aged children. Testicular descent occurs in two phases. During the first phase, before midgestation, testis remains anchored to the inguinal area by insulin like hormone 3 (INSL3)-driven development of the gubernaculum. The second inguinoscrotal phase is dependent on testicular androgens and it is usually completed by the time of birth. Mutations of specific genes have rarely been reported in cryptorchidism. However, several risk factors for cryptorchidism, such as preterm birth and low birth weight, have been described. Environmental factors may also have a role in the etiology of cryptorchidism. Future studies on the gene-environment interaction will give new insights to the pathogenesis of cryptorchidism.

RET(MEN 2B) is active in the endoplasmic reticulum before reaching the cell surface.

MEN 2B (multiple endocrine neoplasia type 2B) is an autosomal dominant cancer syndrome caused by an oncogenic form of the receptor tyrosine kinase REarranged during transfection (RET). The MEN 2B syndrome is associated with an abnormal autophosphorylation of the mutated receptor even without ligand-stimulation. Here, we characterize the activation of a RET(MEN 2B) variant carrying the point mutation Met918Thr, and show that the 150 kDa precursor of RET(MEN 2B) becomes phosphorylated already during synthesis in the endoplasmic reticulum (ER). At least three different tyrosine residues (Tyr905, Tyr1062, Tyr1096) of the RET(MEN 2B) precursor are phosphorylated before the oncogenic receptor reaches the cell surface. We also demonstrate that the precursor of RET(MEN 2B) interacts with both growth factor receptor-bound protein and Src homology 2 domain-containing already in the ER, and that this interaction is dependent on the kinase activity of RET. With the aid of two RET mutants (RET(MEN 2B/S32L) and RET(MEN 2B/F393L)), which accumulate in the ER, we show that the oncogenic precursor of the receptor has the capacity to activate AKT, extracellular signal-regulated kinase and signal transducer and activator of transcription 3 from the ER. Taken together, our data demonstrate that the oncogenic precursor of RET(MEN 2B) is phosphorylated, interacts with adapter proteins and induces downstream signalling from the ER.

Nordic consensus on treatment of undescended testes.

AIM: To reach consensus among specialists from the Nordic countries on the present state-of-the-art in treatment of undescended testicles. METHODS: A group of specialists in testicular physiology, paediatric surgery/urology, endocrinology, andrology, pathology and anaesthesiology from all the Nordic countries met for two days. Before the meeting, reviews of the literature had been prepared by the participants. RECOMMENDATIONS: The group came to the following unanimous conclusions: (1) In general, hormonal treatment is not recommended, considering the poor immediate results and the possible long term adverse effects on spermatogenesis. Thus, surgery is to be preferred. (2) Orchiopexy should be done between 6 and 12 months of age, or upon diagnosis, if that occurs later. (3) Orchiopexy before age one year should only be done at centres with both paediatric surgeons/urologists and paediatric anaesthesiologists. (4) If a testis is found to be undescended at any age after 6 months, the patient should be referred for surgery--to paediatric rather than general surgeons/urologists if the boy is less than one year old or if he has bilateral or non-palpable testes, or if he has got relapse of cryptorchidism.

The effect of authentic metallic implants on the SAR distribution of the head exposed to 900, 1800 and 2450 MHz dipole near field.

As the use of radiofrequency (RF) electromagnetic (EM) fields has increased along with increased use of wireless communication, the possible related health risks have also been widely discussed. One safety aspect is the interaction of medical implants and RF devices like mobile phones. In the literature, effects on active implants like pacemakers have been discussed but the studies of passive metallic (i.e. conductive) implants are rare. However, some studies have shown that the EM power absorption in tissues may be enhanced due to metallic implants. In this study, the effect of authentic passive metallic implants in the head region was examined. A half-wave dipole antenna was used as an exposure source and the specific absorption rate (SAR, W kg(-1)) in the near field was studied numerically. The idea was to model the presumably worst cases of most common implants in an accurate MRI-based phantom. As exposure frequencies GSM (900 and 1800 MHz) and UMTS (2450 MHz) regions were considered. The implants studied were skull plates, fixtures, bone plates and ear rings. The results indicate that some of the implants, under very rare exposure conditions, may cause a notable enhancement in peak mass averaged SAR.

Environmental effects on hormonal regulation of testicular descent.

Regulation of testicular descent is hormonally regulated, but the reasons for maldescent remain unknown in most cases. The main regulatory hormones are Leydig cell-derived testosterone and insulin-like factor 3 (INSL3). Luteinizing hormone (LH) stimulates the secretion of these hormones, but the secretory responses to LH are different: INSL3 secretion increases slowly and may reflect the LH dependent differentiated status of Leydig cells, whereas testosterone response to LH is immediate. Testosterone contributes to the involution of the suspensory ligament and to the inguinoscrotal phase of the descent, while INSL3 acts mainly in transabdominal descent by stimulating the growth of the gubernaculum. INSL3 acts through a G-protein coupled receptor LGR8. In the absence of either INSL3 or LGR8 mice remain cryptorchid. In humans only few INSL3 mutations have been described, whereas LGR8 mutations may cause some cases of undescended testis. Similarly, androgen insensitivity or androgen deficiency can cause cryptorchidism. Estrogens have been shown to down regulate INSL3 and thereby cause maldescent. Thus, a reduced androgen-estrogen ratio may disturb testicular descent. Environmental effects changing the ratio can thereby influence cryptorchidism rate. Estrogens and anti-androgens cause cryptorchidism in experimental animals. In our cohort study we found higher LH/testosterone ratios in 3-month-old cryptorchid boys than in normal control boys, suggesting that cryptorchid testes are not cabable of normal hormone secretion without increased gonadotropin drive. This may be either the cause or consequence of cryptorchidism. Some phthalates act as anti-androgens and cause cryptorchidism in rodents. In our human material we found an association of a high phthalate exposure with a high LH/testosterone ratio. We hypothesize that an exposure to a mixture of chemicals with anti-androgenic or estrogenic properties (either their own activity or their effect on androgen-estrogen ratio) may be involved in cryptorchidism.

Enantiomeric ratios as an indicator of exposure processes for persistent pollutants in human placentas.

The enantiomeric ratios (ER) of alpha-HCH and o,p'-DDT ((+)-isomer concentration/(-)-isomer concentration) and o,p'-DDD (first eluting enantiomer/second enantiomer) were investigated in 112 human placentas from Finnish boys collected 1997-2001. Both o,p'-DDD and alpha-HCH showed changes in their ER depending on the total concentration of the compound in the sample. Their ERs are approaching a value close to racemic mixture (ER=1) at high concentrations. At low concentrations they often differ from 1. The relationship between concentration and ER is clearly identified and it has been shown that it is not affected by analytical uncertainty. This relationship appears to be important for assessing tissue- and species-specific exposure and risk and it may indicate whether net uptake or metabolic activity is dominant in exposure for the resulting exposure of the enantiomers.

Patient education and health-related quality of life: surgical hospital patients as a case in point.

The purpose of this study was to analyze the connections between patient education and health-related quality of life as an outcome variable. Data were collected among surgical hospital patients (n = 237) in Finland. On the basis of the results, there seems to be a positive relationship between received knowledge and health-related quality of life, and as such, the study produced knowledge about one quality indicator in nursing care. More research is needed to explore this connection in greater details.

Testicular dysgenesis syndrome and the development and occurrence of male reproductive disorders.

Patients with 45,X0/46XY karyotype often present with intersex phenotype and testicular dysgenesis. These patients may also have undescended testes (cryptorchidism), hypospadias and their spermatogenesis is severely disrupted. They have a high risk for testicular cancer. These patients have the most severe form of testicular dysgenesis syndrome (TDS). We have hypothesized that testicular cancer, cryptorchidism, hypospadias and poor spermatogenesis are all signs of a developmental disturbance that was named as testicular dysgenesis syndrome. The hypothesis is based on clinical and epidemiological findings and on biological and experimental evidence. Signs of TDS share several risk factors, such as small birth weight (particularly being small for gestational age), and they are risk factors for each other. All of them have background in fetal development. They show strong epidemiological links so that countries with high incidence of testicular cancer, such as Denmark, tend to also have high prevalence rates of cryptorchidism and hypospadias and poor semen quality. Vice versa, in countries with good male reproductive health, e.g., in Finland, all these aspects are better than in Denmark. Although genetic abnormalities can cause these disorders, in the majority of cases, the reasons remain unclear. Adverse trends in the incidence of male reproductive disorders suggest that environmental and life style factors contribute to the problem. Endocrine disrupters are considered as prime candidates for environmental influence. Fetal exposure to high doses of dibutyl phthalate was shown to cause a TDS-like phenotype in the rats. Studies are underway to assess whether there is any exposure-outcome relation with selected chemicals (persistent organic pollutants, pesticides, phthalates) and cryptorchidism.

Interaction of mobile phones with superficial passive metallic implants.

The dosimetry of exposure to radiofrequency (RF) electromagnetic (EM) fields of mobile phones is generally based on the specific absorption rate (SAR, W kg(-1)), which is the electromagnetic energy absorbed in the tissues per unit mass and time. In this study, numerical methods and modelling were used to estimate the effect of a passive, metallic (conducting) superficial implant on a mobile phone EM field and especially its absorption in tissues in the near field. Two basic implant models were studied: metallic pins and rings in the surface layers of the human body near the mobile phone. The aim was to find out 'the worst case scenario' with respect to energy absorption by varying different parameters such as implant location, orientation, size and adjacent tissues. Modelling and electromagnetic field calculations were carried out using commercial SEMCAD software based on the FDTD (finite difference time domain) method. The mobile phone was a 900 MHz or 1800 MHz generic phone with a quarter wave monopole antenna. A cylindrical tissue phantom models different curved sections of the human body such as limbs or a head. All the parameters studied (implant size, orientation, location, adjacent tissues and signal frequency) had a major effect on the SAR distribution and in certain cases high local EM fields arose near the implant. The SAR values increased most when the implant was on the skin and had a resonance length or diameter, i.e. about a third of the wavelength in tissues. The local peak SAR values increased even by a factor of 400-700 due to a pin or a ring. These highest values were reached in a limited volume close to the implant surface in almost all the studied cases. In contrast, without the implant the highest SAR values were generally reached on the skin surface. Mass averaged SAR(1 g) and SAR(10 g) values increased due to the implant even by a factor of 3 and 2, respectively. However, at typical power levels of mobile phones the enhancement is unlikely to be problematic.

Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries.

BACKGROUND: Several investigators have shown striking differences in semen quality and testicular cancer rate between Denmark and Finland. Since maldescent of the testis is a shared risk factor for these conditions we undertook a joint prospective study for the prevalence of congenital cryptorchidism. METHODS: 1068 Danish (1997-2001) and 1494 Finnish boys (1997-99) were consecutively recruited prenatally. We also established prevalence data for all newborns at Turku University Central Hospital, Finland (1997-99, n=5798). Testicular position was assessed by a standardised technique. All subtypes of congenital cryptorchidism were included, but retractile testes were considered normal. FINDINGS: Prevalence of cryptorchidism at birth was 9.0% (95% CI 7.3-10.8) in Denmark and 2.4% (1.7-3.3) in Finland. At 3 months of age, prevalence rates were 1.9% (1.2-3.0) and 1.0% (0.5-1.7), respectively. Significant geographic differences were still present after adjustment for confounding factors (birthweight, gestational age, being small for gestational age, maternal age, parity, mode of delivery); odds ratio (Denmark vs Finland) was 4.4 (2.9-6.7, p<0.0001) at birth and 2.2 (1.0-4.5, p=0.039) at three months. The rate in Denmark was significantly higher than that reported 40 years ago. INTERPRETATION: Our findings of increasing and much higher prevalence of congenital cryptorchidism in Denmark than in Finland contribute evidence to the pattern of high frequency of reproductive problems such as testicular cancer and impaired semen quality in Danish men. Although genetic factors could account for the geographic difference, the increase in reproductive health problems in Denmark is more likely explained by environmental factors, including endocrine disrupters and lifestyle.