Paternal p,p'-DDE exposure and pre-pubertal high-fat diet increases the susceptibility to fertility impairment and sperm Igf2 DMR2 hypo-methylation in male offspring.

The hypothesis of paternal origins of health and disease (POHaD) indicates that paternal exposure to adverse environment could alter the epigenetic modification in germ line, increasing the disease susceptibility in offspring or even in subsequent generations. p,p'-Dichlorodiphenyldichloroethylene (p,p'-DDE) is an anti-androgenic chemical and male reproductive toxicant. Gestational p,p'-DDE exposure could impair reproductive development and fertility in male offspring. However, the effect of paternal p,p'-DDE exposure on fertility in male offspring remains uncovered. From postnatal day (PND) 35 to 119, male rats (F0) were given 10 mg/body weight (b.w.) p,p'-DDE or corn oil by gavage. Male rats were then mated with the control females to generate male offspring. On PND35, the male offspring were divided into 4 groups according whether to be given the high-fat diet (HF): corn oil treatment with control diet (C-C), p,p'-DDE treatment with control diet (DDE-C), corn oil treatment with high-fat diet (C-HF) or p,p'-DDE treatment with high-fat diet (DDE-HF) for 35 days. Our results indicated that paternal p,p'-DDE exposure did not affect the male fertility of male offspring directly, but decreased sperm quality and induced testicular apoptosis after the high-fat diet treatment. Further analysis demonstrated that paternal exposure to p,p'-DDE and pre-pubertal high-fat diet decreased sperm Igf2 DMR2 methylation and gene expression in male offspring. Hence, paternal exposure to p,p'-DDE and pre-pubertal high-fat diet increases the susceptibility to male fertility impairment and sperm Igf2 DMR2 hypo-methylation in male offspring, posing a significant implication in the disease etiology.

Parental transgenerational epigenetic inheritance related to dietary crude oil exposure in Danio rerio.

Transgenerational inheritance from both parental lines can occur by genetic and epigenetic inheritance. Maternal effects substantially influence offspring survival and fitness. However, investigation of the paternal contribution to offspring success has been somewhat neglected. In the present study, adult zebrafish were separated into female and male groups exposed for 21 days to either a control diet or to a diet containing water accommodated fractions of crude oil. Four F1 offspring groups were obtained: (1) control (non-exposed parents), (2) paternally exposed, (3) maternally exposed and (4) dual-parent-exposed. To determine the maternal and paternal influence on their offspring, we evaluated responses from molecular to whole organismal levels in both generations. Growth rate, hypoxia resistance and heart rate did not differ among parental groups. However, global DNA methylation in heart tissue was decreased in oil-exposed fish compared with control parents. This decrease was accompanied by an upregulation of glycine N-methyltransferase. Unexpectedly, maternal, paternal and dual exposure all enhanced survival of F1 offspring raised in oiled conditions. Regardless of parental exposure, however, F1 offspring exposed to oil exhibited bradycardia. Compared with offspring from control parents, global DNA methylation was decreased in the three offspring groups derived from oil-exposed parents. However, no difference between groups was observed in gene regulation involved in methylation transfer, suggesting that the changes observed in the F1 populations may have been inherited from both parental lines. Phenotypic responses during exposure to persistent environmental stressors in F1 offspring appear to be influenced by maternal and paternal exposure, potentially benefitting offspring populations to survive in challenging environments.

Prenatal Exposure to Environmentally-Relevant Contaminants Perturbs Male Reproductive Parameters Across Multiple Generations that are Partially Protected by Folic Acid Supplementation.

The paternal environment is thought to influence sperm quality and future progeny may also be impacted. We hypothesized that prenatal exposure to environmentally-relevant contaminants impairs male reproduction, altering embryo gene expression over multiple generations. Folic acid (FA) can improve sperm quality and pregnancy outcomes, thus we further hypothesized that FA mitigates the contaminants. Sprague-Dawley F0 female rats treated with persistent organic pollutants (POPs) or corn oil and fed basal or supplemented FA diets, then used to yield four generations of litters. Only F0 females received POPs and/or FA treatments. In utero POPs exposure altered sperm parameters in F1, which were partly rescued by FA supplementation. Paternal exposure to POPs reduced sperm quality in F2 males, and the fertility of F3 males was modified by both POPs and FA. Ancestral FA supplementation improved sperm parameters of F4 males, while the POPs effect diminished. Intriguingly, F3 males had the poorest pregnancy outcomes and generated the embryos with the most significantly differentially expressed genes. Early-life exposure to POPs harms male reproduction across multiple generations. FA supplementation partly mitigated the impact of POPs. The two-cell embryo transcriptome is susceptible to paternal environment and could be the foundation for later pregnancy outcomes.

Maternal, but not paternal or grandparental, caffeine intake is associated with childhood obesity and adiposity: The Lifeways Cross-Generation Cohort Study.

BACKGROUND: Maternal caffeine intake is associated with adverse birth outcomes, but its long-term influence on offspring adiposity outcomes is not well studied. Furthermore, few studies have investigated paternal and grandparental caffeine intake in relation to offspring outcomes. OBJECTIVE: To study the associations between maternal, paternal, and grandparental caffeine intake and offspring childhood adiposity. DESIGN: The core study sample consists of 558 mother-child pairs from the Lifeways Study. Caffeine intake was derived from relevant food items in a self-administered validated food frequency questionnaire in early pregnancy. Children's body mass index (BMI) and waist circumference (WC) were measured at 5- and 9-y follow-up. Childhood overall and central obesity were defined as age- and sex-specific BMI z-score > International Obesity Task Force cut-off and WC z-score > 90th percentile, respectively. Multiple linear and logistic regressions were used to assess associations. RESULTS: Study mothers had a mean age of 30.8 y and a mean prepregnancy BMI (kg/m2) of 23.7. In adjusted models, maternal caffeine intake was associated with a higher offspring BMI z-score [ß (95% CI): 0.13 (0.06, 0.21) for year 5 and 0.17 (0.04, 0.29) for year 9; per 100 mg/d increment in maternal caffeine intake], WC z-score [ß (95% CI): 0.09 (0.01, 0.17) for year 5 and 0.19 (0.05, 0.32) for year 9], and a higher risk of offspring overall obesity [OR (95% CI): 1.32 (1.11, 1.57) for year 5 and 1.44 (1.10, 1.88) for year 9] and central obesity [1.28 (1.02, 1.60) for year 5 and 1.62 (1.12, 2.34) for year 9]. The influence was stronger for coffee caffeine than tea caffeine. No consistent associations were observed for paternal and grandparental caffeine intake. CONCLUSIONS: Maternal antenatal, but not paternal or grandparental, caffeine intake is associated with higher offspring adiposity and obesity risk at age 5 and 9 y, with stronger associations observed for coffee caffeine. This prospective observational study was registered at the ISRCTN Registry as ISRCTN16537904.

Parental occupational exposure to solvents and heavy metals and risk of developing testicular germ cell tumors in sons (NORD-TEST Denmark).

Objective The present study aims to assess if parental occupational exposure to solvents or heavy metals is associated with risk of testicular germ cell tumors (TGCT) in sons in Denmark. Methods The NORD-TEST Denmark included 3421 cases diagnosed with TGCT at ages 14-49 years in Denmark between 1981 and 2014. Controls (N=14 024) selected from the central population registry were matched to cases on birth year. The Danish Supplementary Pension Fund provided parental occupational information. A job-exposure matrix was used to assign exposures, and conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results The overall analyses showed no significant associations except for paternal exposure to a sub-group of "heavy metal(s) and solvent(s)" (OR 1.50, 95% CI 1.01-2.24). Most fathers in this category had worked in wood related jobs and were assigned exposure to chromium VI and toluene. Other sub-group analyses suggested that maternal exposure to aromatic hydrocarbon were associated with TGCT risk, in sons born in 1970-1979, and to heavy metals (chromium, iron and nickel) in sons born in 1980-1998. Conclusion NORD-TEST Denmark provides no strong support for an association between parental exposures to solvents or heavy metals and TGCT in sons, and only weak support for an association between paternal exposure to chromium and toluene and TGCT risk in sons.

Spinal nerve defects in mouse embryos prenatally exposed to valproic acid.

To examine in detail spinal nerve defects induced by prenatal exposure to valproic acid in mice, pregnant ICR mice were subcutaneously injected with a single dose of 400 mg/kg valproic acid on gestational day 6, 7, 8, or 9, and their embryos were observed on gestational day 10. The whole-mount immunostaining using an anti-neurofilament antibody allowed us to identify spinal nerve defects, such as a loss of bundle, anastomosis among bundles arising from adjacent segment, and a disrupted segmental pattern of the dorsal root ganglia, in valproic acid-exposed embryos. The prevalence of spinal nerve defects was the highest in the embryos exposed to valproic acid on gestational day 8 among the experimental groups. Then, effects of the administration dose of valproic acid on the prevalence of spinal nerve defects were examined on gestational day 10 and found to be dose-dependently increased. It was noteworthy that all embryos exposed to 600 mg/kg of valproic acid on gestational day 8 suffered spinal nerve defects. Folic acid (3 mg/kg/day) supplementation during gestational day 6-10 suppressed the prevalence of valproic acid-induced neural tube defects, which are common malformations in offspring prenatally exposed to valproic acid, but not that of spinal nerve defects. Thus, the spinal nerve defects due to prenatal valproic acid exposure might be induced by mechanisms different from those of neural tube defects. Because spinal nerve defects were predicted to be caused by the disrupted segmental arrangement of the somites and/or that of neural crest cells, which was the origin of the dorsal root ganglia and/or abnormal polarity of the somite, this mouse model with spinal nerve defects at high incidence would be useful to examine the effects of valproic acid on the somitogenesis and morphogenesis of somite-associated structures.

A paternal diet for offspring success?

Supplementation of the diet of male mice with methyl donors, such as methionine and folic acid, prior to mating impaired learning, memory, and metabolic functions in the offspring.

Systematic review of the association between oil and natural gas extraction processes and human reproduction.

This systematic review identified 45 original published research articles related to oil and gas extraction activities and human reproductive endpoints. Reproductive outcomes were categorized as [1] birth outcomes associated with maternal exposure, [2] semen quality, fertility, and birth outcomes associated with adult paternal exposure, [3] reproductive cancers, and [4] disruption of human sex steroid hormone receptors. The results indicate there is moderate evidence for an increased risk of preterm birth, miscarriage, birth defects, decreased semen quality, and prostate cancer. The quality of the evidence is low and/or inadequate for stillbirth, sex ratio, and birth outcomes associated with paternal exposure, and testicular cancer, female reproductive tract cancers, and breast cancer, and the evidence is inconsistent for an increased risk of low birth weight; therefore, no conclusions can be drawn for these health effects. There is ample evidence for disruption of the estrogen, androgen, and progesterone receptors by oil and gas chemicals, which provides a mechanistic rationale for how exposure to oil and gas activities may increase the health risks we have outlined. The results from this systematic review suggest there is a negative impact on human reproduction from exposure to oil and gas activities. Many of the 45 studies reviewed identified potential human health effects. Most of these studies focused on conventional oil and gas activities. Few studies have been conducted to evaluate the impact of unconventional oil and gas operations on human health. The impact of unconventional oil and gas activities may be greater than that of conventional activity, given that unconventional activities employ many of the same approaches and use dozens of known endocrine-disrupting chemicals in hydraulic fracturing.

Parental risk factors of anorectal malformations: Analysis with a regional population-based control group.

BACKGROUND: Adequate evidence on environmental risk factors for anorectal malformations (ARMs) is very limited. We assessed maternal body weight and several prenatal exposures of the parents to tobacco, pregestational diabetes, chronic cardiovascular and respiratory diseases, periconceptional folic acid and multivitamin intake. METHODS: Data from the German Network for Congenital Uro-REctal malformations (CURE-Net) were compared with data from the Malformation Monitoring Centre Saxony-Anhalt of the Otto-von-Guericke University in Magdeburg, Germany. Controls were matched to cases by gender and birth year of the child. Crude and adjusted odds ratios (95% confidence intervals) were calculated for potential risk factors using multivariable logistic regression. RESULTS: In total, 158 ARM patients and 474 healthy infants born between 1993 and 2008 in Germany were included. Maternal age at birth of ARM cases and birth plurality were significantly higher and gestational age and weight significantly lower compared with controls (p < 0.0001). We observed significantly increased risks for ARMs associated with maternal smoking before conception and the first trimester of pregnancy (odds ratio = 2.23, 95% confidence interval 1.04-4.79, p = 0.039) and maternal chronic respiratory diseases (odds ratio = 29.25, 95% confidence interval 8.22-104.14, p < 0.0001). No statistically significant increased risk or protective effect was found for the other investigated factors. CONCLUSION: This study suggests an association between the occurrence of ARMs in the offspring and periconceptional maternal smoking as well as maternal chronic respiratory diseases. In addition, there might be a sign of an association for maternal diabetes, although not statistically significant. It can be assumed that the power is far too low to provide reliable estimates.

Association of Parental Environmental Exposures and Supplementation Intake with Risk of Nonsyndromic Orofacial Clefts: A Case-Control Study in Heilongjiang Province, China.

The aim of present study was to check the possible association of potential parental environmental exposures and maternal supplementation intake with the risk of nonsyndromic orofacial clefting (NSOC). A retrospective study comprised 499 cases and 480 controls was conducted in Heilongjiang Province. Chi-square analysis and unconditional multiple logistic regression were used in the study. The results showed that maternal history of fever and the common cold without fever (ORCL/P = 3.11 and 5.56, 95%CI: 1.67-5.82 and 2.96-10.47, ORCPO = 3.31 and 8.23, 95%CI: 1.58-6.94 and 4.08-16.95), paternal smoking and alcohol consumption (ORCL/P = 2.15 and 5.04, 95%CI: 1.37-3.38 and 3.00-8.46, ORCPO = 1.82 and 4.40, 95%CI: 1.06-3.13 and 2.50-7.74), maternal exposure to organic solvents, heavy metals, or pesticides (ORCL/P = 6.07, 5.67 and 5.97, 95%CI: 1.49-24.76, 1.34-24.09 and 2.10-16.98, ORCPO = 10.65, 7.28 and 3.48, 95%CI: 2.54-44.67, 1.41-37.63 and 1.06-11.46) and multivitamin use during the preconception period (ORCL/P = 0.06, 95%CI: 0.02-0.23, ORCPO = 0.06, 95%CI: 0.01-0.30) were associated with cleft lip or without cleft palate (CL/P) and cleft palate only (CPO). Maternal history of skin disease and negative life events (ORCL/P = 12.07 and 1.67, 95%CI: 1.81-80.05 and 1.95-2.67) were associated with CL/P. Some potential parental hazardous exposures during the periconception period and maternal use of multivitamins during the preconception period were associated with risk of NSOC.

Genes underlying positive influence of prenatal environmental enrichment and negative influence of prenatal earthquake simulation and corrective influence of Chinese herbal medicine on rat offspring: Irf7 and Ninj2.

BACKGROUND: Prenatal environmental enrichment (EE) has been proven to positively affect but prenatal stress negatively influence the physiological and psychological processes in animals, whose trans-generational genetic mechanism remains unclearly defined. We aimed to investigate and find out key genes underlying the positive-negative effects derived from prenatal interventions. MATERIALS AND METHODS: Pregnant rats were randomized into EE group (EEG), earthquake simulation group (ESG), herbal group (HG) received herbal supplements in feed after earthquake simulation, and control group (CG). RESULTS: Light Box Defecation Test (LBDT) showed EEG offspring presented less fecal pellets than CG offspring, ESG's more than CG's, and HG's less than ESG (p's<0.05). Open-field Test (OFT) score of EEG was higher than CG offspring, of ESG's was lower than CG's, and HG's higher than ESG's. Irf7 and Ninj were screened, which were up-regulated in EEG, down-regulated in ESG (FC<0.5), and were neutralized in HG. Prenatal EE could positively promote the nervous system development, prenatal earthquake simulation could retard the nervous system development and Chinese herbal remedy (JKSQW) which could correct the retardation. CONCLUSION: The negative-positive prenatal effect could contribute to altered gene expression of Irf7 and Ninj2 which also could play a key role in the improving function of JKSQW for the kidneys.

[The impact of male phytoestrogenization on the somato-sexual development and fertility of the offsprings in rats].

The effect of phytoestrogen-rich diet administered to male rats in a dose 20 mg/kg of body weight for 30 days with the mixture of phytoestrogens on reproductive function of male offspring and the effect of additional phytoestrogenization during milk feeding have been investigated. It was shown that male phytoestrogenization leads to feminization of the offsprings. Specifically, at birth, the ano-genital distance in males was less than that measured in control rats: (2.7 +/- 0.1) vs (3.1 +/- 0.0) mm (P < 0.05). This and additional phytoestrogenization of newborn rats during milk feeding inhibit their somatic and sexual development, weakening sexual activity in adults and reducing fertility at the expense of dectreased fertilizing capacity of sperm. A possible mechanism for the observed effects may be a reduction of relative androgenization due to increased of estradiol concentration by 3-4 times. Analysis of the data revealed a significant impact of phytoestrogens in father's diet on reproductive function of their offsprings under conditions of additional phytoestrogenization after birth.

Parental olfactory experience influences behavior and neural structure in subsequent generations.

Using olfactory molecular specificity, we examined the inheritance of parental traumatic exposure, a phenomenon that has been frequently observed, but not understood. We subjected F0 mice to odor fear conditioning before conception and found that subsequently conceived F1 and F2 generations had an increased behavioral sensitivity to the F0-conditioned odor, but not to other odors. When an odor (acetophenone) that activates a known odorant receptor (Olfr151) was used to condition F0 mice, the behavioral sensitivity of the F1 and F2 generations to acetophenone was complemented by an enhanced neuroanatomical representation of the Olfr151 pathway. Bisulfite sequencing of sperm DNA from conditioned F0 males and F1 naive offspring revealed CpG hypomethylation in the Olfr151 gene. In addition, in vitro fertilization, F2 inheritance and cross-fostering revealed that these transgenerational effects are inherited via parental gametes. Our findings provide a framework for addressing how environmental information may be inherited transgenerationally at behavioral, neuroanatomical and epigenetic levels.

Reproductive effects of low-to-moderate medical radiation exposure.

Medical radiation from x-rays and nuclear medicine is the largest man-made source of radiation exposure in Western countries, accounting for a mean effective dose of 3.0 mSv per capita per year, comparable to the radiologic risk of 150 chest x-rays, and in many cases gonads fall in the imaging field, with > 20 millions examinations per year in US being abdominal and pelvic CT, and > 0.5 million barium enema. Of the over 7 million workers exposed to medical radiation, special attention has been paid to those working in the interventional cardiology and radiology labs, with high and increasing professional exposures, two-to three times higher than diagnostic radiologists. Thus, adverse effects of radiation exposure are well worth of the scientific community's interest. Aims of this review are: 1) to assess gonad dose to patients undergoing diagnostic testing or interventional fluoroscopy therapy and in professionally exposed interventional fluoroscopists; and 2) to evaluate the evidence linking radiation exposure in the low-to-moderate range (besides the radiotherapy high dose range) to adverse reproductive effects. In patients, the gonad radiation exposure can reach 5 mSv for a lower limb angiography, 20 mSv for a CT pelvis and hips, and 36 (in females) to 90 mSv (for males) for a lower gastrointestinal series. For interventional cardiologists, the gonad dose (below lead apron) is in the same order of magnitude of the shielded thyroid dose, with a median of 50 to 100 microSievert per cine-angiography procedure. The dose can be ten-fold higher for a complex interventional procedure. This leads to a cumulative exposure in the 0.5-1 Sv range over a professional lifetime of 30 years. At present, the epidemiological approach provided inconclusive results, inadequate for a robust evidence-based advice to exposed subjects, since large groups followed-up for decades would be required to detect a small increase in risk. A molecular epidemiology approach and/or the use of integrated biomarkers of reproductive health (e.h., reproductive hormone balance, sperm quality, sperm DNA damage) might be more fruitful in future research focused in the low-to-moderate dose range (< 1000 mSv) of greatest interest for diagnostic and professional exposures.

Congenital fibrosarcoma and history of prenatal exposure to petroleum derivatives.

Congenital fibrosarcoma (CFS) is a rare fibrous tissue malignancy that usually presents in the first few years of life. It is unique among human sarcomas in that it has an excellent prognosis. We describe a temporal clustering of a number of cases of CFS and investigate the possible associated prenatal risk factors. The Pediatric Environmental History, a questionnaire developed in our clinic that is instrumental in determining environmental risk factors for tumor-related disease, was essential in documenting the presence or absence of risk factors considered as human carcinogens. We found a history of exposure to petroleum products in four cases of CFS that occurred at a greater than expected rate in a short time frame-an apparent cancer cluster. We call attention to the possibility that exposure to petroleum products raises the risk of developing CFS. While future studies should focus on systematic investigation of CFS and its underlying mechanisms, this report suggests the need for proactive measures to avoid exposure to solvents and petroleum products during pregnancy.

Periconceptional folate deficiency and implications in neural tube defects.

Nutritional deficiencies are preventable etiological and epigenetic factors causing congenital abnormalities, first cause of infant mortality. Folate deficiency has a well-established teratogenic effect, leading to an increasing risk of neural tube defects. This paper highlights the most recent medical literature about folate deficiency, be it maternal or paternal. It then focuses on associated deficiencies as nutritional deficiencies are multiple and interrelated. Observational and interventional studies have all been consistent with a 50-70% protective effect of adequate women consumption of folates on neural tube defects. Since strategies to modify women's dietary habits and vitamin use have achieved little progress, scientific as well as political effort is mandatory in order to implement global preventive public health strategies aimed at improving the alimentation of women in reproductive age, especially folic acid supplementation. Even with the recent breakthrough of fetal surgery for myelomeningocele, the emphasis should still be on prevention as the best practice rather than treatment of neural tube defects.

Effect of astragaloside IV on the general and peripartum reproductive toxicity in Sprague-Dawley rats.

Fertility and early embryonic developmental toxicity in rats were evaluated by intravenously administering astragaloside IV (AS-IV) daily at 0.25, 0.5, and 1.0 mg/kg for 4 weeks before mating, throughout the mating period, and continuing to day 6 of gestation period in females. Perinatal toxicity in rats was evaluated on gestational days (GD) 15 to 21 and lactational days LD (LD) 1 to 21. Astragaloside IV had no maternal toxicity at 0.25 to 1.0 mg/kg in rats. Although it has an inhibitory effect on female fertility in F0/F1 rats, AS-IV was devoid of early embryonic developmental toxicity in F0/F1 rats and in the survival parameters of F1 postnatal rats. Maternal AS-IV exposure at the dose of 1.0 mg/kg per d resulted in a significant delay in time for fur development, eye opening, and cliff parry reflex of pups compared to control group (P < .05), whereas it did not affect the memory and learning of F1 pups.

Preconceptional paternal exposure to depleted uranium: transmission of genetic damage to offspring.

Depleted uranium (DU) is an alpha particle emitter and radioactive heavy metal used in military applications. Due to internalization of DU during military operations and the ensuing chronic internal exposure to DU, there are concerns regarding its potential health effects. Preconceptional paternal irradiation has been implicated as a causal factor in childhood cancer and it has been suggested that this paternal exposure to radiation may play a role in the occurrence of leukemia and other cancers to offspring. Similarly, in vivo heavy metal studies have demonstrated that carcinogenic effects can occur in unexposed offspring. Using a transgenic mouse system employing a lambda shuttle vector allowing mutations (in the lacI gene) to be analyzed in vitro, we have investigated the possibility that chronic preconceptional paternal DU exposure can lead to transgenerational transmission of genomic instability. The mutation frequencies in vector recovered from the bone marrow cells of the F1 offspring of male parents exposed to low, medium, and high doses of internalized DU for 7 mo were evaluated and compared to control, tantalum, nickel, and gamma radiation F1 samples. Results demonstrate that as paternal DU-dose increased there was a trend towards higher mutation frequency in vector recovered from the DNA obtained from bone marrow of F1 progeny; medium and high dose DU exposure to P1 fathers resulted in a significant increase in mutation frequency in F1 offspring (3.57 +or - 0.37 and 4.81 + or - 0.43 x 10; p < 0.001) in comparison to control (2.28 + or - 0.31 x 10). The mutation frequencies from F1 offspring of low dose DU, Ta- or Ni-implanted fathers (2. 71 + or - 0.35, 2.38 + or - 0.35, and 2.93 + or - 0.39 x 10, respectively) were not significantly different than control levels (2.28 + or - 0.31 x 10). Offspring from Co (4 Gy) irradiated fathers did demonstrate an increased lacI mutation frequency (4.69 + or - 0.48 x 10) as had been shown previously. To evaluate the role of radiation involved in the observed DU effects, males were exposed to equal concentrations (50 mg U L) of either enriched uranium or DU in their drinking water for 2 mo prior to breeding. A comparison of these offspring indicated that there was a specific-activity dependent increase in offspring bone marrow mutation frequency. Taken together these uranyl nitrate data support earlier results in other model systems showing that radiation can play a role in DU-induced biological effects in vitro. However, since the lacI mutation model measures point mutations and cannot measure large deletions that are characteristic of radiation damage, the role of DU chemical effects in the observed offspring mutation frequency increase may also be significant. Regardless of the question of DU-radiation vs. DU-chemical effects, the data indicate that there exists a route for transgenerational transmission of factor(s) leading to genomic instability in F1 progeny from DU-exposed fathers.

Paternal work stress and prolonged time to pregnancy.

OBJECTIVE: The aim of this study was to explore an association between psychosocial stress at work in married men and their spouses' prolonged time to pregnancy (TTP). METHODS: All married male workers of a large Korean petrochemical enterprise and their wives fulfilling the selection criteria were included. Main selection criteria were lack of use of contraceptives and experienced pregnancy in recent past. Data were available from 322 couples. Psychosocial stress at work was measured by the effort-reward imbalance questionnaire. Prolonged TTP was measured by the "TTP questionnaire". RESULTS: After adjustment for confounding effects of demographic and life-style characteristics and benzene exposure, delayed TTP, defined by frequency of first-cycle pregnancy, was associated with one standard deviation (SD) increase of the effort-reward ratio in the chronically stressed group of married men (OR = 0.47; 95% CI = 0.22-0.99) in logistic regression analysis. A similar, but somewhat weaker effect, was found for the overall group (OR = 0.67; 95% CI = 0.47-0.94). CONCLUSIONS: Paternal stress at work, as measured by effort-reward imbalance, seemed to be associated with a decreased number of conceptions in the first menstrual cycle.

Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy and childhood malignant central nervous system tumours: the ESCALE study (SFCE).

Parental smoking and maternal alcohol and caffeinated beverage consumption are prevalent exposures which may play a role, either directly or through their influence on metabolism, in the aetiology of childhood malignant central nervous system (CNS) tumours. The hypothesis was investigated in the Epidemiological Study on childhood Cancer and Leukemia ESCALE study, a national population-based case-control study carried out in France in 2003-2004. The study included 209 incident cases of CNS tumours and 1681 population-based controls, frequency matched with the cases by age and sex. The data were collected through a standardized telephone interview of the biological mothers. No association between maternal smoking during pregnancy and CNS tumours [odds ratio (OR): 1.1 (0.8-1.6)] was observed. Paternal smoking during the year before birth was associated with CNS tumours (P for trend=0.04), particularly astrocytomas [OR: 3.1 (1.3-7.6)]. Maternal alcohol consumption during pregnancy was not associated with CNS tumours. Associations between ependymomas and the highest consumption of coffee [OR: 2.7 (0.9-8.1)] and tea [OR: 2.5 (1.1-5.9)] were observed. A strong association between CNS tumours and the highest maternal consumption of both coffee and tea during pregnancy was observed [OR: 4.4 (1.5-13)]. The results constitute additional evidence for a role of paternal smoking and suggest that maternal coffee and tea consumption during pregnancy may also increase the risk of CNS tumours. The study does not suggest an increased risk of CNS tumours related to alcohol consumption during pregnancy.