Genetic polymorphisms of ESR1 and ESR2 that may influence estrogen activity and the risk of hypospadias.

BACKGROUND: The etiology of hypospadias is regarded as a complex disorder with both genetic and environmental contributions. Although alterations in androgen activity have been associated with hypospadias, few associations with estrogen activity have been documented. Here, we assessed genetic polymorphisms in estrogen receptor genes and their association with hypospadias. METHODS: Using a case-control study of 59 cases with hypospadias and 286 controls, we examined the association of hypospadias with the following polymorphisms: PvuII and XbaI in ESR1, and 2681-4A>G in ESR2. RESULTS: For the cases, we found a negative association with the G allele containing variants of ESR1 XbaI (OR = 0.52, P < 0.05), and a negative association with the G allele containing variants of ESR2 2681-4A>G (OR = 0.59, P < 0.05). For the cases, we also identified a negative association with the CG haplotype, and a positive association with the CA haplotype, defined by ESR1 PvuII and XbaI (P < 0.05). CONCLUSIONS: These findings suggest that the G allele containing variants of ESR1 XbaI and the G allele containing variants of ESR2 2681-4A>G may decrease the risk of hypospadias, whereas the ESR1 C-A haplotype may increase its risk.

Parental and neonatal risk factors for cryptorchidism.

BACKGROUND: Cryptorchidism is one of the most common congenital malformations in males. As male sexual differentiation is critically dependent on normal androgen concentrations, increased exposure to environmental factors affecting androgen homeostasis during fetal life may cause cryptorchidism. We investigated the relation between cryptorchidism and lifestyle, occupational exposure and the characteristics of parents and/or the perinatal and delivery characteristics. MATERIAL/METHODS: Case-control study conducted among the eligible 96 cases underwent orchiopexy between 1990 and 2003 and 116 controls were enrolled among boy outpatients born in between 1985 and 2001 and who were determined by pediatricians not to have genitourinary malformation. All the cases and controls were surveyed between 1999 and 2003 in Japan. RESULTS: We found significant positive associations between cryptorchidism and cesarean section (OR=2.19, 95% CI=1.09-4.40), paternal smoking before and during pregnancy (OR=1.87, 95% CI=1.03-3.37 and OR=1.94, 95% CI=1.08-3.50, respectively) and paternal exposure to diesel exhaust before and during pregnancy (OR=2.42, 95% CI=1.06-5.55 and OR=2.35, 95% CI=0.99-5.59, respectively). CONCLUSIONS: We found associations of cryptorchidism with unusual delivery and paternal smoking during pregnancy. These findings suggested that cryptorchidism might be associated with not only genetic factors but also increased parental exposure to environmental factors. In the future, prospective study is needed to do risk assessment accurately in the hormone-dependent stages of pregnancy critical for testicular descent.

[Exposure to endocrine disrupting chemicals and human health: a review of epidemiological studies focused on hypospadias and cryptorchidism].

Hypospadias and cryptorchidism are common congenital anomalies. Recently, increases in the prevalence of hypospadias and cryptorchidism have been reported in various countries, including Japan. As male sexual differentiation is critically dependent on normal androgen concentrations, increased exposure to environmental factors affecting androgen homeostasis during fetal life (i.e. EDCs with estrogenic or anti-androgenic effects) may cause hypospadias or cryptorchidism. However, the results from the International Clearinghouse for Birth Defects Monitoring System (ICBDMS), hospital-based studies in each country and population-based studies in Japan are different, because in the present system there are some problems such as the standardization of diagnostic criteria and the difference of the time of diagnosis, we hope to improve the monitoring system method. Previous papers have reported that hypospadias and cryptorchidism were associated with maternal exposure to progesterone, estrogen, diethylstilbestrol (DES) and pesticide. However, there are few studies evaluating the quantity of endocrine disrupting chemicals, using biological samples. In the future, a well-designed epidemiological study is needed to elucidate the relation between endocrine disrupting chemicals and genital development.

The estimated prevalence of hypospadias in Hokkaido, Japan.

BACKGROUND: Hypospadias is one of the most common congenital anomalies in the world. Recently, increases in the prevalence of hypospadias have been reported in various countries including Japan. In this study, we examined whether the prevalence of hypospadias in Hokkaido, Japan, increased or not, using standardized diagnostic criteria. We also investigated the degree of its severity. METHODS: We calculated prevalence of hypospadias using hospital records of hypospadias repair in Hokkaido. The prevalence from 1985 through 1997 by dividing the number of patients obtained from hospital records by the number of births. RESULTS: The average prevalence of hypospadias in Hokkaido was 3.9 per 10,000 births, and did not significantly change (p=0.7). The average proportions of distal, proximal and chordee alone were 56.7%, 39.6% and 3.7%, respectively. The decrease in the proportion of the proximal type was statistically significant (p=0.05) for the entire time period, whereas the proportion of the distal type did not have a significant upward trend for the observed 13 years (p=0.1). CONCLUSION: No significant changes in the prevalence of hypospadias existed in Hokkaido.

Urinary catecholamines and salivary cortisol on workdays and days off in relation to job strain among female health care providers.

OBJECTIVES: This study examined the effects of psychosocial job strain on the excretion of neuroendocrine stress hormones (adrenaline, noradrenaline, and cortisol) on workdays and days off. METHODS: Japanese female health care providers (N=16) filled out Karasek's job content questionnaire and had their neuroendocrine excretions (ie, urinary catecholamines and salivary cortisol) measured on a day off and on two workdays (one day shift and one night shift). After control for age and job experience as covariates, a repeated-measures analysis of variance was carried out. RESULTS: Noradrenaline excretion was significantly greater over time in the high-strain group than in the low-strain group, and that of the high-demand group was significantly greater over time than that of the low-demand group. Adrenaline excretion did not significantly differ between the groups. The group with high supervisory support had significantly higher adrenaline excretion than the group with low supervisory support. The concentration of salivary cortisol on a dayshift was significantly lower, but marginally, in the high-strain group than in the low-strain group. CONCLUSIONS: Psychosocial job strain is associated with greater noradrenaline excretion over time. This finding suggests unwinding sympathetic nervous activity. The low cortisol levels of the high-strain group may indicate circadian rhythm disturbance induced by job strain. Supervisory relationships may have a particular influence for the studied occupation because the participants had more administrative contact with supervisors than support at the worksite; therefore, supervisory support may increase adrenaline excretion.

Visual dysfunction in workers exposed to a mixture of organic solvents.

The aim of this study was to investigate the relationship between the workers occupationally exposed to a mixture of organic solvents and their visual functions. Here the visual functions included color vision (CV), visual contrast sensitivity (CS) and visual evoked potentials (VEP). Test subjects were 182 workers at 53 furniture factories in the same industrial area of Japan. As control, a group consisted of 96 workers without exposure to any organic solvent was also tested. Exposure assessments were made both by the environmental concentration and biological monitoring. CV and CS tests were carried out for all the subjects. VEP was measured for 21 exposed subjects who were considered to have impaired CV and CS. In the results, the color confusion index (CCI) values of the exposed subjects were significantly higher than that of the age-matched controls (P<0.01). Their CS values were significantly lower than those in the controls at spatial frequencies of 6 and 12 cycles per degree (cpd) (P<0.01 and <0.05, respectively). A significant correlation between the concentration of urinary methylhippuric acid and contrast sensitivity was found by a multiple regression analysis (P<0.05). CCI showed a negative correlation at all spatial frequencies of CS in a simple regression analysis, no abnormal data were found by the VEP test in the exposed subjects who were found to have impaired CV and CS. The results suppose that a low concentration of the mixed organic solvents might affect the retina and optic nerve. However, it needs to be further researched if such an impact affects the Brodmann's areas of visual cortex in the brain.

Work-related reproductive, musculoskeletal and mental disorders among working women--history, current issues and future research directions.

According to the recent changes of working environments and socio-economical conditions, the proportion of working women are increasing in Japan. Characteristics of occupational workload and stress of Japanese working women are consistent with those in many industrialized countries except man-dominant culture. In this review we describe the history, current issues, and future research directions on occupational health of working women, especially focused on reproductive health, work-related musculo-skeletal disorders (WMSDs), and mental disorders. In the reproductive health survey, traditionally main concern was about pregnancy outcomes, then fecundity studies, such as time to pregnancy, became topics recently. Future research will be shifted to outcomes not only during pregnancy but also disorders of hormonal balance and climacterium or health conditions after menopause. WMSDs are reviewed on mainly gender difference and its causative factors. Historically, mental health of working women in Japan has focused on the job stress of nurses. We compare results with a lot of recent researches in Europe and U.S.A., where interaction between occupational stress and family roles were studied. It is not easy to predict the prospective status of female workers in Japan, but social, workplace and familial supports will enhance their health promotion.