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At least 19 recordsLinked to original sources
PubMed2000

Paternal exposure to lead and infertility.

To assess whether paternal exposure to lead is associated with infertility, we performed a register-based study among married men biologically monitored for exposure to inorganic lead. We obtained information about the marriages and the wives of the men from the Finnish Central Population Register. Data on pregnancies were obtained from medical records. Paternal exposure to lead was assessed on the basis of blood lead measurements. We estimated the risk of infertility, defined as nonoccurrence of a marital pregnancy, by applying binomial regression. For the blood lead categories of 0.5-0.9, 1.0-1.4, 1.5-1.9, 2.0-2.4, and > or =2.5 micromol/L the relative risk of infertility, compared with the risk in the lowest exposure category (<0.5 micromol/L), was 1.27 (95% confidence interval 1.08-1.51), 1.35 (1.12-1.63), 1.37 (1.08-1.72), 1.50 (1.08-2.02), and 1.90 (1.30-2.59), respectively. The findings support the hypothesis that paternal exposure to lead increases the risk of infertility at low occupational exposure levels. We applied proportional hazards regression to the analysis of pregnancy delay. A delay was observed among the wives of men exposed to lead. Exposure to lead was not clearly associated with delayed pregnancy, however, when the analysis was restricted to couples with at least one pregnancy. This finding suggests that the restriction of the study on time to pregnancy to fertile couples may introduce a bias toward no association.

Adult↗
PubMedDate not supplied

Paternal exposure of rabbits to lead: behavioral deficits in offspring.

Paternal exposures to exogenous agents have been reported to produce a variety of developmental defects in the offspring. In experimental animals, these effects include decreased litter size and weight, increased stillbirth and neonatal death, birth defects, tumors, and functional/behavioral abnormalities-some of these effects being transmitted to the second and third generations. The majority of experimental studies assessing nervous system function of offspring following paternal exposures have utilized rats as the experimental animal, but other species can be used. The National Toxicology Program (NTP) has initiated studies to validate the rabbit as an animal model for human reproductive toxicity, because rabbits are the smallest laboratory animal from which ejaculates can be collected repeatedly. An important part of reproductive toxicology is assessment of the reproductive ability of males following exposure, as well as developmental and functional assessment of their offspring. This article describes a pilot study and a main study to investigate the feasibility of using rabbits to assess the functional effects of paternal exposure to lead. The pilot study included seven male rabbits per group exposed for 15 weeks to lead acetate sufficient to produce 0, 50, or 110 micrograms/dl blood lead. The main study included 15 male rabbits per group exposed for 15 weeks to lead acetate to produce 0, 20, 40, and 80 micrograms/dl blood lead. At the conclusion of the exposure, male rabbits were mated with unexposed females. These females carried their litters to term, delivered, and reared their own offspring. The offspring were weighed at 5, 10, 15, 20, 25, 30, and some at 35 days of age. They were also tested for exploratory activity in a standard figure-eight "maze" for 30 min/day on days 15, 20, 25, and 30. A second assessment of exploratory behavior, along with a simple test of aversive conditioning, was attempted in the pilot study, but was judged not to be suitable for the main study. Of the 21 male rabbits that were mated in the pilot study, 16 produced viable litters (6/7, 6/7, and 4/7 in control, low- and high-lead groups, respectively), with a mean number of 6 live births/litter in each treatment group (range 2-8). Of the 60 rabbits mated in the main study, 57 produced litters, and two rabbits died giving birth. Significant postnatal deaths were observed in all groups, with about one half of the offspring dying before testing was initiated at day 15. There were no treatment-related effects on offspring weight gain through wearing. The data suggest that paternal lead exposure of rabbits may reduce figure-eight activity on day 25, the time of peak activity in the offspring.

Analysis of Variance↗
PubMed2005

Impact of paternal exposure to chemotherapy on offspring in the rat.

Paternal exposure to chemotherapeutics may have adverse effects on offspring. In the rat, chronic low-dose paternal exposure to the anticancer drug cyclophosphamide increased pre- and postimplantation loss and malformations. The effects of paternal drug treatment on progeny were influenced by the stage when germ cells were first exposed. Chronic cyclophosphamide treatment resulted in a dramatic decrease in the expression of stress response genes in pachytene spermatocytes and round spermatids but not in elongated spermatids; reduced gene expression may allow damage to accumulate. Exposure for 9 weeks, but not for 6, increased the incidence of aneuploidy. DNA strand breaks were maximal 3 weeks after short-term or acute treatment, during spermiogenesis. Cyclophosphamide-exposed spermatozoa imparted DNA damage to the fertilized embryo. Total RNA synthesis was higher in one-cell embryos sired by drug-treated fathers than in controls, and the expression of specific genes was altered. Thus, in the rat, paternal exposure to an anticancer drug altered germ cell quality, disrupting embryo development and dysregulating zygotic gene activation.

Animals↗
PubMed1988

Human mutagens: evidence from paternal exposure?

The importance of inherited mutations as a cause of human disease has been established clearly through examples of well-defined genetic anomalies, such as Down syndrome and retinoblastoma. Furthermore, it is suspected that environmental contaminants induce mutations resulting in increased risk for such defects in subsequent generations of persons exposed. The present lack of direct evidence for induced inherited genetic disorders in human beings hampers the development of risk estimation techniques for extrapolation from animal models. The most extensive prospective epidemiologic studies of inherited genetic effects have involved survivors of atomic bomb detonations and patients treated with cancer chemotherapy. In neither case has a significant elevation in inherited genetic effects or cancer been detected in the offspring of exposed individuals. Epidemiologic studies of subjects receiving chronic exposure may be confounded by the effect of maternal exposure during pregnancy. Consideration of only paternal exposure can minimize the confounding influence of teratogenicity, enhancing the resolving power of studies for inherited effects. Using this approach, retrospective (case-control) studies of childhood cancer patients have provided limited but suggestive evidence for inheritance of induced effects. Endpoints, such as congenital malformations and spontaneous abortion following paternal exposure, can also be considered as indicators of heritable mutagenic effects. For example, there is limited evidence suggesting that paternal exposure to anaesthetic gases may cause miscarriage and congenital abnormalities as a result of induced male germ cell mutations. By comparing male-exposure endpoints for which there are human data, as described above, with parallel or similar animal endpoints, such as dominant lethal, inherited cancer and "male teratogenic" effects, it is possible that suitable models for extrapolating to human risk can be developed. In order to establish a clearer relationship between induced mutation and genetic disease, the current surveillance systems should be expanded to include endpoints relevant to genetic study. The relaxation of regulations regarding access to census data could improve the chances of documenting such an association.

Abortion, Spontaneous↗
PubMed1993

Paternal exposures and cardiovascular malformations. The Baltimore-Washington Infant Study Group.

Possible associations between paternal exposures and cardiovascular malformations were evaluated in the Baltimore-Washington Infant Study, a population based case-control investigation of congenital heart disease and environmental factors. Home interviews of case and control parents elicited information on parental home and occupational exposures. Analysis focused on twelve cardiac diagnostic groups and paternal exposures incurred during the six months preceding the pregnancy. Associations were identified between jewelry making and atrial septal defect (Odds ratio: 12.6; 95% confidence interval: 2.3-68.6) and membranous ventricular septal defect (8.1; 2.0-33.3), welding and endocardial cushion defect with Down syndrome (1.8; 1.1-3.0), lead soldering and pulmonary atresia (2.3; 1.1-4.9) and ionizing radiation and endocardial cushion defect without Down syndrome (4.7; 1.7-12.6). Ionizing radiation was found to be associated with endocardial cushion defect with Down syndrome only when father was present at interview (5.6; 1.7-17.9); a similar effect of father at interview was noted for paint stripping in relation to coarctation of the aorta (3.5; 1.5-8.0) and muscular ventricular septal defect (3.5; 1.5-8.5). Also, paint stripping was associated with hypoplastic left heart only in the presence of family history of cardiac defects (11.9; 2.4-60.0). This large study on cardiac diagnostic groups and specific preconceptional exposures provides new leads for further assessment of the role of paternal exposures on adverse pregnancy outcome.

Adult↗
PubMed1998

Paternal exposure to pesticides and congenital malformations.

OBJECTIVES: A case-referent study with 261 matched pairs was carried out in 8 hospitals of Comunidad Valenciana, Spain, to assess the relation between occupational exposure to pesticides and selected congenital malformations. In this paper, the results concerning paternal exposure are presented. METHODS: The parents of the case patients and the referents were interviewed to collect information about exposure to pesticides and potential confounding variables. Detailed information on direct involvement in the handling of pesticides was collected for the interviewees involved in agricultural activities during a previously defined period in relation to conception and pregnancy. Exposure data were reviewed by 2 experts who assigned ordinal scores for the probability and intensity of exposure to pesticide classes and active ingredients. RESULTS: The dichotomous analysis of exposure (absent, present) yielded some increased risks, although not statistically significant, for aliphatic hydrocarbons [adjusted odds ratio (adjusted OR) 2.05, 95% confidence interval (95% CI) 0.62-6.80], inorganic compounds (adjusted OR 2.02, 95% CI 0.53-7.72), and glufosinate (adjusted OR 2.45, 95% CI 0.78-7.70), and a significant association for pyridil derivatives (adjusted OR 2.77, 95% CI 1.19-6.44). The analysis based on the experts' scores (2 levels of exposure) showed some consistent associations for these compounds. CONCLUSIONS: This research indicates a possible risk of congenital malformations for paternal exposure to some pesticides, notably, pyridils, aliphatic hydrocarbons, inorganic compounds, and glufosinate. It did not find an increased risk for paternal exposure to pesticides in the classes of organophosphates, carbamates, organochlorines, chloroalkylthio fungicides and organosulfurs. These findings warrant further investigation.

Agriculture↗
PubMed2000

Paternal exposure to cyclophosphamide alters cell-cell contacts and activation of embryonic transcription in the preimplantation rat embryo.

Paternal exposure to chronic low doses of cyclophosphamide, an anticancer agent, results in aberrant embryonic development of the progeny. We hypothesized that paternal exposure to cyclophosphamide disturbs zygotic gene activity regulating proper progression through preimplantation development and that this disturbance results in improper cell-cell interactions. To test this hypothesis, we analyzed cell-cell interactions and the expression of cytoskeletal elements in preimplantation embryos sired by male rats gavaged with saline or 6 mg kg(-1) day(-1) cyclophosphamide for 5 wk. Embryos from control litters had 4-12 cells on Day 2 of gestation; cell-cell contacts were observed consistently. Embryos from litters sired by cyclophosphamide-treated males were frequently abnormal and had lower cell numbers and decreased cell-cell contacts. Steady state concentrations of the mRNAs for cell adhesion molecules (cadherins and connexin 43) and structural proteins (beta-actin, collagen, and vimentin) were low in two- and four-cell control embryos; expression increased dramatically by the eight-cell stage. In contrast, embryos sired by cyclophosphamide-treated males displayed the highest expression of most trancripts at the two-cell stage. In parallel with the mRNA profiles, E-cadherin immmunoreactivity was nearly absent in two-cell control embryos and was strong by the eight-cell stage; immunoreactivity in embryos sired by drug-treated fathers was strong at the two-cell stage but absent at later stages. Thus, drug exposure of the paternal genome led to dysregulated expression of structural elements and decreased cell interactions during preimplantation embryonic development.

Animals↗
PubMed1993

Childhood cancer and paternal exposure to ionizing radiation: preliminary findings from the Oxford Survey of Childhood Cancers.

Paternal occupational data already collected as part of the Oxford Survey of Childhood Cancers have been reviewed. Information on occupations during or before the relevant pregnancy was sought for 15,279 children dying from cancer in England, Wales, and Scotland in the period 1953-81, and for an equal number of matched controls. Estimates were made for paternal exposure to human-made external ionizing radiation in the six months before conception of the survey child--as judged from job histories and dates of birth. Assessments were also made for potential exposure to unsealed sources of radionuclides. Of the eight fathers placed in the highest dose group (> or = 10 mSv, external radiation), four were cases and four were controls. For the second dose group (5-9 mSv), the corresponding numbers were eight and four, and for the lowest exposed group (1-4 mSv), they were 55 and 42. There were 27 case fathers with potential exposure to radionuclides and only 10 control fathers. The independent effects of the two radiation variables were assessed by means of multiple logistic regression. Relative risks for estimated doses of external radiation were close to unity, but for radionuclide exposure the relative risk was 2.87 (95% CI = 1.15-7.13). These preliminary findings suggest that paternal exposure to radionuclides is a more likely risk factor for childhood cancer than exposure to external radiation.

Adult↗
PubMed1999

Influence of paternal exposure to oil and oil products on time to pregnancy and spontaneous abortions.

The objective of this study was to evaluate the influence of exposure to oil and oil products among men on the time taken for their wives to conceive and on the incidence of spontaneous abortion among them. A cross-sectional study was performed by posting questionnaires to 1,269 men employed as offshore mechanics, offshore operators, offshore drilling personnel, car mechanics (the 'exposed' occupations) and carpenters ('unexposed'). The married men were asked to give a separate questionnaire to their wives for details about their pregnancies. The time elapsed between the beginning of coitus without contraception and the wife becoming pregnant (time to pregnancy) was analyzed with Cox regression analysis by calculating fecundability ratios for the pregnancies for the men exposed to oil and oil products as compared with the men who were not exposed. Spontaneous abortions were analyzed with logistic regression by calculating odds ratios for the pregnancies in which the men were exposed vs. not exposed. A total of 741 (58%) men returned the questionnaires. A total of 301 pregnancies were analyzed for time taken to conceive and 580 for spontaneous abortion. The results were adjusted for variables that could significantly influence conception time (previous infections of the reproductive system and coffee drinking) or the incidence of spontaneous abortion (mother's age, parity and smoking). The outcomes between the exposed and unexposed pregnancies showed no significant differences. Car mechanics had a lower fecundability ratio before 1992 than after 1992. Paternal exposure to hydrocarbons in the occupations studied did not seem to have had a major influence on time to conception or the incidence of spontaneous abortion among the wives of the men exposed to oil products.

Abortion, Spontaneous↗
PubMed1994

Occupational paternal exposure to benzene and risk of spontaneous abortion.

OBJECTIVE: The purpose of this study was to evaluate the risk of spontaneous abortion among the wives of male workers occupationally exposed to benzene. METHODS: The wives of 823 men working in two chemical plants at the time of the study were asked to complete a questionnaire describing their pregnancies. The analysis of the 1739 pregnancies that ended in a spontaneous abortion or a birth is presented. The firms' payroll records provided all workers' employment history, including dates. Benzene exposure, graded at two levels (< 5, > or = 5 ppm), was determined for every job, so that benzene exposure for each worker's entire professional life (at these companies) could be assessed. This information was linked to the dates of the pregnancies reported in the questionnaires to enable the exposure status of each pregnancy to be defined (1270 non-exposed and 274 exposed). The frequency of spontaneous abortion, defined as the number of spontaneous abortions divided by the total of spontaneous abortions and births was evaluated. RESULTS: When adjusted for tobacco consumption, mother's age and pregnancy order, the odds ratio of the association between paternal exposure to approximately 5 ppm of benzene and the risk of spontaneous abortion was close to and statistically not different from unity (OR = 1.1; 95% CI (0.7-1.8). CONCLUSION: In this study paternal exposure to benzene did not increase the risk of spontaneous abortion.

Abortion, Spontaneous↗
PubMed1996

Reproductive effects of paternal exposure to chlorophenate wood preservatives in the sawmill industry.

OBJECTIVES: The purpose of the study was to determine whether paternal occupational exposure to dioxincontaminated chlorophenols is associated with an increased risk of congenital anomalies or other adverse reproductive outcomes in offspring. METHODS: As a result of a multistep linkage, 19675 births between 1952 and 1988 were identified as children of a cohort of 9512 fathers who had worked at least one year in British Columbia sawmills where chlorophenate wood preservatives had been used. A nested case-referent analysis was applied, using conditional logistic regression, with five referents matched per case according to year of birth and gender. Chlorophenate exposure was based on expert raters' estimations of hours of exposure applied to specific time windows prior to birth. RESULTS: The offspring of male sawmill workers were at increased risk for developing congenital anomalies of the eye, particularly congenital cataracts; elevated risks for developing anencephaly or spina bifida and congenital anomalies of genital organs were shown according to specific windows of exposure. No associations were found for low birthweight, prematurity, stillbirths, or neonatal deaths. CONCLUSIONS: The study adds further support to the hypothesis of male-mediated developmental toxicity. Paternal exposure to chlorophenates was associated with the development of certain congenital anomalies in offspring.

Abnormalities, Drug-Induced↗
PubMed2003

Developmental toxicity of in ovo exposure to polychlorinated biphenyls: II. Effects of maternal or paternal exposure on second-generation nestling american kestrels.

The development of second-generation nestling American kestrels (Falco sparverius) was altered by in ovo exposure of only one parent to polychlorinated biphenyls (PCBs). Polychlorinated biphenyls appear to alter nestling development through both maternally and paternally mediated effects. In 1998, F0 parent kestrels consumed approximately 5 to 7 microg total PCBs/g bird/d (Aroclors 1248:1254: 1260) for approximately 100 d prior to eggs hatching; these eggs, containing total PCB concentrations of 34.1 microg/g, produced 13 F1 offspring, which were then paired in 1999 with unexposed kestrels to examine developmental effects of maternal or paternal in ovo PCB exposure. Using a toxicokinetics model, eggs from the maternally exposed group had predicted PCB levels of 0.03 to 0.34 microg/g, with enriched higher chlorinated congeners. Polychlorinated biphenyl concentrations in eggs of all generations have recently been found in eggs and nestlings of free-ranging eagles. Consistent with the first generation, maternally exposed F2 females generally were larger, had altered growth rates, and delayed maximal growth and fledging compared with control females. Maternally exposed F2 males were heavier but had shorter bones, grew more quickly and earlier, and fledged 2 d later than control males. In the maternally exposed group, concentrations of plasma triiodothyronine were elevated in F2 females but suppressed in F2 males. Paternally exposed F2 hatchlings of both sexes were comparable in size to controls with the exception of having longer tarsi bones, but subsequently showed slower, delayed growth (both sexes) and fledging (females) and lower thyroxine concentrations (males). The alterations in thyroid hormones in the F2 generation are discussed in light of the enrichment of higher chlorinated PCB congeners and hydroxylated PCB congeners. The developmental changes in the kestrel nestlings are likely a function of several possible mechanisms involving maternal PCB deposition, parental behavior, and neurobehavioral and endocrine-thyroid function in nestlings.

Animals↗
PubMed2000

Paternal exposure to cyclophosphamide dysregulates the gene activation program in rat preimplantation embryos.

Although there has been progress in determining the mechanisms by which maternal toxicant exposure affects progeny, there is little information on the actions of drugs administered to the father. We investigated the effects of pre-conceptional paternal exposure to cyclophosphamide, an anti-cancer agent, on embryonic gene activation in the rat. The male pronucleus was formed earlier in embryos sired by cyclophosphamide-treated male rats than in those sired by controls; early male pronucleus formation was followed by alterations in the gene activation program. BrUTP incorporation into RNA and Sp1 transcription factor immunostaining were increased and spread over both cytoplasmic and nuclear compartments in 2-cell embryos sired by cyclophosphamide-treated males compared to controls. Total RNA synthesis was constant in 1-8 cell embryos sired by drug-treated fathers, while in control embryos RNA synthesis increased four-fold to peak at the 4-cell stage. In 2-cell embryos sired by drug-treated males, the relative abundance of candidate imprinted genes was elevated significantly above control; a peak in the expression of these genes was not observed until the 8-cell stage in control embryos. Thus, paternal drug exposure temporally and spatially dysregulated rat zygotic gene activation, altering the developmental clock.

Animals↗
PubMedDate not supplied

Paternal exposures and the question of birth defects.

Compared to maternal exposures, little attention has been paid to the possibility of paternally induced adverse effects on fetal development. There is increasing concern, however, about the potential for male-mediated developmental toxicity brought about by exposure to teratogenic agents. This is evidenced by the number of calls regarding paternal exposures that are received by teratogen information services. In this paper, we report the experience of the state of Florida's Teratogen Information Services regarding questions asked about paternal exposures, and briefly review what is known about the risk of paternal exposure to the 10 agents which are most frequently queried.

Abnormalities, Drug-Induced↗
PubMed1996

Paternal exposures: impact on reproductive and developmental outcome. An overview.

Experimental and epidemiologic investigations document the adverse consequences of an array of paternal exposures on the development of subsequent offspring. Male-mediated abnormalities have been reported after exposure to therapeutic and recreational drugs, to chemicals in the workplace and environment and to ionizing radiation. The impact on progeny outcome includes: an increase in congenital malformations, spontaneous abortions, fetal resorptions; low birth weight; increase in childhood cancers; developmental, neurobehavioral, neuroendocrine, neurochemical abnormalities; effects in F2 generation progeny. Fertility is often unaffected. The comparative influence of genetic, epigenetic and nongenetic mechanisms in the etiology of paternally-mediated adverse outcomes is unknown. There is no a priori reason to assume that male-mediated effects are limited to the agents studied to date. The broad spectrum of alterations recorded after exposure to a variety of unrelated agents suggests the need for a more focused effort and multidisciplinary exploration of the potential impact of the male parent on reproductive outcome.

Animals↗
PubMedDate not supplied

Effects of limited paternal exposure to xenobiotic agents on the development of progeny.

This report represents a series of investigations of the postnatal functional sequelae of paternal exposure to opioids and other xenobiotic agents. In separate studies, young adult male mice were exposed to (1) morphine; (2) levorphanol or its nonanalgesic isomer dextrorphan; or (3) 80% nitrous oxide/20% oxygen. Males (5-8/group) were injected twice daily for 5 1/2 or 8 1/2 days with opioids or saline, or received a single 4 hour inhalation exposure to nitrous oxide/oxygen or compressed air. At 6-8 1/2 days post-treatment, each male was housed with 3 drug-naive nulliparous females. With the exception of birth weights of litters, no alterations in reproductive indices were observed. Changes in reproductive endocrine parameters included marked attenuation of serum luteinizing hormone response to castration in both young adult (8 week) and older (18 week) F1 morphine offspring, when compared with saline-derived groups. The morphine progeny showed decrements in body weight and delayed onset of maturational indices through four generations of selective inbreeding. Similar developmental delays occurred in F1 offspring originating from paternal levorphanol, dextrorphan and nitrous oxide groups, when compared with their respective controls. Behavioral study of F1 offspring revealed alterations in: water maze performance and learning, if preceded by unavoidable footshock, in morphine offspring at 8 and 18 weeks; aberrant swim patterns in both levorphanol and dextrorphan progeny at 6 1/2 and 8 1/2 weeks. Nitrous oxide progeny showed a blunting of hypothermic response to pharmacologic challenge at 16 weeks, in comparison to compressed air controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗