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PubMed2002

Fetotoxicity caused by the interaction between zinc and arsenic in mice.

Arsenic is an environmental pollutant that induces congenital malformations in experimental models and can contribute to human birth defects. The environmental exposure to arsenic is relatively small when compared with the doses required to cause teratogenicity in mice and other laboratory animals. In order to study the action of zinc in the arsenic-induced teratogenicity, in the present work mice were either pretreated with zinc and later with arsenic or were treated simultaneously with zinc and arsenic in vivo and in vitro. Following administration of arsenate on gestation day 8, pregnant females were killed on the 17th day of gestation; maternal and fetal data were collected by laparotomy and used to calculate reproductive parameters. Fetuses were analyzed for the presence of external malformation and, after the appropriate processing, visceral and skeletal analyses were accomplished. Conceptuses were exposed in whole embryo culture to arsenicals on gestation day 8 (3-6 somite stage). After a 26 h culture period, morphological development was assessed. Neither pretreatment with zinc nor simultaneous administration of zinc prevented arsenic teratogenicity in these experimental models.

Abnormalities, Drug-Induced↗

PubMed1995

Evaluation of the OECD 421 reproductive toxicity screening test protocol using 1-(butylcarbamoyl)-2-benzimidazolecarbamate (benomyl).

The OECD 421 reproductive toxicity screening test protocol was evaluated using the fungicide benomyl as a test compound at 10, 30, or 90 mg/kg per day. Male rats showed dose-dependent testicular degeneration after 28 days exposure, as expected on the basis of literature data. Dams in the high dose group, exposed from 14 days premating to postnatal day 6, had pups with decreased weights at postnatal days 1 and 6. Prenatal deaths were increased, but no malformations were found. In contrast, in a developmental toxicity test with exposure between gestation days 6 and 15, 90 mg/kg induced a high level of postimplantation loss, with ophthalmic malformations in the surviving offspring, in agreement with literature data. It is suggested that premating exposure in the OECD 421 protocol may have induced tolerance to the compound, e.g., by modulation of biotransformation in the dam. These findings indicate that the teratogenic potential of a compound need not necessarily be revealed using this screening test. The OECD 421 protocol appeared sufficiently sensitive to reveal the reproductive hazard of benomyl on the basis of prenatal deaths and testicular and pup weight effects. However, the absence of congenital anomalies in the offspring after benomyl treatment according to the OECD 421 protocol underscores the notion that lack of biological activity in the test should not be regarded as evidence of lack of activity of a compound on reproductive parameters.

Animals↗

PubMed1984

Teratology of intravaginally administered contraceptive jelly containing octoxynol-9 in rats.

Octoxynol-9, a nonionic surfactant used as a spermicidal agent in ORTHO-GYNOL (registered trademark) Contraceptive Jelly (Ortho Pharmaceutical Corporation, Raritan, NJ), was administered intravaginally to pregnant Sprague Dawley COBS CD rats at dosages of 0.5 mg/kg/day and 5 mg/kg/day (two-thirds and six times the clinical dosage) on days 6-15 of gestation in order to assess its teratogenic potential. Untreated, sham, and vehicle control groups were also incorporated into the study protocol. No meaningful differences were observed between the treated and control groups in maternal toxicity, maternal reproductive parameters, fetal toxicity, and the incidence of external, visceral, and skeletal malformations or developmental variations. It is concluded that octoxynol-9 is not embryotoxic or teratogenic when administered intravaginally to rats during organogenesis.

Abnormalities, Drug-Induced↗

PubMed1984

Fetal alcohol syndrome in the ferret (Mustela putorius).

Gastric intubation of 1.5 g ethanol/kg maternal body weight produced a significant teratogenic response in ferrets (Mustela putorius) treated once daily from gestational days 15 through 35. This response was evident by a rise in the frequency of fetuses with one or more malformations (21%), and by a rise in the frequency of litters with one or more malformed fetuses (50%). Palatoschisis and greater relative intermedial canthi distance observed in this study are diagnostic features of the fetal alcohol syndrome (FAS). Although mean (+/- SEM) peak blood alcohol levels of 207 +/- 9 mg/dl did not affect other reproductive parameters, high doses of alcohol (3.0 g/kg) resulted in the inability of treated females to consume adequate food or water, in the complete resorption of litters, and in significant maternal mortality (88%). Fetal deaths occurred prior to gestation day 17 in the high-dose alcohol group. Based on objective evaluation of differences among ethanol-treated, pair-fed sucrose-treated, and untreated ad libitum diet controls, the ferret would seem a valuable alternative animal species for future studies of FAS.

Animal Diseases↗

PubMed1992

Effects of a 48 hour continuous intravenous infusion of CGS 13080-primagrel, a selective thromboxane synthetase inhibitor, on the perinatal and early postnatal period in the guinea pig.

CGS 13080, imidazo[1,5-a]pyridine-5-hexanoic acid, was evaluated for perinatal and postnatal effects in third trimester pregnant guinea pigs and their offspring. The compound was administered via 48 hour continuous intravenous infusion to a group of pregnant guinea pigs (n = 16) at a dose of 3 mg/kg/hr starting on gestational day 52 (via chronically implanted indwelling jugular venous cannulas). A saline control group (n = 12) received equivalent volumes of normal saline 0.5 ml/kg/hr throughout the dosing period. A third group (surgery-sham, n = 16) was subjected to cannulation but not infused. A gross examination of each dam and piglets was conducted at necropsy on day 5 of lactation. The neonatal brains and all gross lesions (maternal and neonatal) were removed and fixed for histopathological examination. Compound-related clinical signs were noted in dams during the dosing phase of gestation. Six guinea pigs developed cephalic lymphatic swelling during the infusion. This observation may be correlated to the reported redistribution of fluid volume to the thorax of guinea pigs given intravenous injections of CGS 13080. There were no compound-induced effects on labor, delivery, or any of the examined reproductive parameters. There were no compound-related clinical signs, or effects on survival, body weight and developmental parameters in the F1 generation. Histopathological examination of the brains and other organs did not reveal any compound-related abnormalities. Based on these results, it was concluded that CGS 13080 did not elicit adverse perinatal and postnatal effects in guinea pigs.

Animals↗

PubMed2002

Reproductive potential of crimson-spotted rainbowfish (Melanotaenia fluviatilis) following short-term exposure to bass strait crude oil and dispersed crude oil.

An examination of the potential of crude oil and mixtures of dispersants and crude oil to act as reproductive toxicants is reported in this article. The short-term effects of a water-accommodated fraction of crude oil (WAF) and a dispersed crude oil water-accommodated fraction (DCWAF) on selected reproductive end points were measured by conducting 3-day exposures to the crimson-spotted rainbowfish (Melanotaenia fluviatilis). Exposures were followed by 14-day depuration periods to determine the ability of fish to recover from the exposure. There were no changes to egg production, hatchability, or larval lengths for the WAF and DCWAF test periods. There were no changes to plasma estradiol or testosterone concentrations, gonadosomatic indices, or histopathological organization of gonad tissues after the exposure and depuration periods for both WAF and DCWAF. As reproductive parameters were not altered after 3 days of exposure and 14 days of depuration, crimson-spotted rainbowfish were able to endure short-term exposures to crude oil and dispersed crude oil.

Animals↗

PubMed1999

Key environmental human health issues in the Great Lakes and St. Lawrence River basins.

In May 1997, Health Conference '97-Great Lakes/St. Lawrence, an international conference on the effects of the environment on human health in the Great Lakes and St. Lawrence River basins, was held in Montreal, Québec, Canada. This was the third international conference on this topic sponsored by agencies in the United States and Canada. More than 120 platform and poster presentations were given by scientists of different disciplines from the Great Lakes region and elsewhere. The presentations represented the most current research findings on the effects of the Great Lakes environment on human health. The reports covered environmental contaminant levels of persistent toxic substances (PTSs), routes and pathways of exposure, exposure assessment and human tissue levels of PTSs, human health outcomes, risk communication and assessment, and approaches to scientific collaboration. Reports indicate that levels of contaminants in the Great Lakes and St. Lawrence River basins have generally declined since the 1970s, although certain contaminants have plateaued or slightly increased. The findings include elevated body burden levels of contaminants in persons who consume large amounts of some Great Lakes sport fish, developmental deficits and neurologic problems in children of some fish-consuming parents, nervous system dysfunction in adults, and disturbances in reproductive parameters. The findings underscore the need for better public health intervention strategies.

Adult↗

PubMed2001

Effects of prenatal styrene exposure on postnatal development and brain serotonin and catecholamine levels in rats.

Maternal reproductive effects in Wistar rats exposed to 0, 50, or 300 ppm styrene for 6 h/day during gestational days 6 to 20 were evaluated. Their offspring were observed postnatally for neurochemical changes, growth, and physical landmarks of development. Mothers exposed to styrene were compared with pair-fed and ad-lib-fed controls in order to adjust nutrient conditions. Prolongation of the gestational period, food intake, and the number of neonatal deaths or stillbirths in 300-ppm-exposed dams showed evidence of styrene-related effects. Other reproductive parameters, such as litter size, birth weight, and sex ratio, were found to exhibit no effects within the variation range studied. A neurochemical effect was observed in that the 5-HT and HVA concentrations in cerebrum were significantly decreased. Incisor eruption (mandible), eye opening, and the air-righting reflex were delayed in rat pups born to dams receiving 300 ppm styrene exposure compared with the pair-fed and ad lib control groups. Pups born to dams exposed to 50 ppm styrene also had a significantly delayed air-righting reflex compared with ad lib controls. These results suggest that the offspring were susceptible to the effects of styrene on a few developmental landmarks even when nutritional effects were controlled.

Animals↗

PubMed1993

Mate choice and reproductive success in the red-legged partridge (Alectoris rufa).

Behavioral patterns, reproductive success, and concentrations of plasma-luteinizing hormone, testosterone, and estrogen were compared in pairs of red-legged partridges which had either selected their own mates or had been randomly paired. Males in self-selected pairs called more frequently than males in non-self-selected pairs. Females in self-selected pairs but not those in non-self-selected pairs guarded their nests. Females in self-selected pairs had a greater egg production and laid more of their eggs in nests than females in non-self-selected pairs. There was a significant difference between the two groups in the concentration of plasma testosterone in males, which was higher in males from self-selected pairs prior to the onset of egg laying. These results are consistent with the hypothesis that mate choice affects both reproductive parameters and nest defense in monogamous birds.

Animals↗

PubMed1997

Mortality During Dispersal an the Stability of a Metapopulation

We use a coupled map lattice to investigate the dynamics of a system of populations linked by dispersal, when dispersal incurs an additional mortality cost. Considering a single isolated population first, we show analytically that imposing an additional mortality term can stabilise the non-trivial steady state only under certain conditions. We demonstrate algebraically that in the absence of mortality during dispersal, linking a number of similar populations does not affect whether or not the equilibrium will be stable, although it can affect the nature of any unstable dynamics. Adding a fixed mortality rate during dispersal has a strong stabilising effect on system dynamics. We show analytically that for any combination of intrinsic reproduction parameters, a range of dispersal rates and dispersal mortalities can be found which together act to stabilise the equilibrium. Our results are shown numerically to be robust against a number of perturbations. Hence dispersal mortality has a strong stabilising effect on dynamics. In natural systems, some losses during long-distance dispersal are likely, and so we suggest that this factor could be an important determinant of the strength of observed population fluctuations. Copyright 1997 Academic Press Limited

Journal Article↗

PubMed1999

Normal reproductive organ development in Wistar rats exposed to bisphenol A in the drinking water.

Bisphenol A (BPA) is a chemical used primarily as a monomer in the manufacture of numerous chemical products, such as epoxy resins and polycarbonate. The objective of this study was to evaluate potential effects of BPA on sexual development of male rats and was designed to clarify low-dose observations reported as preliminary results by Sharpe et al. (1996). The protocol for the present study followed the same treatment schedule as reported by Sharpe et al. (1995, 1996), but included more treatment groups, a greater number of animals per group, and a more comprehensive number of reproductive endpoints. Groups of 28 female Han-Wistar albino rats were exposed to drinking water that contained 0, 0.01, 0.1, 1.0, or 10 ppm BPA or 0.1 ppm diethylstilbestrol (DES), 7 days per week, for a total of 10 weeks. Treatment of the females began at 10 weeks of age and continued throughout a 2-week premating period, 2 weeks of mating (to untreated males), 21-22 days of gestation, and 22 days of lactation. Offspring weanling males were given untreated drinking water and maintained until 90 days of age when evaluations were made of various reproductive organs. Consistent with Sharpe et al. (1996) the female offspring were not evaluated. No treatment-related effects on growth or reproductive endpoints were observed in adult females exposed to any concentration of BPA. Similarly, no treatment-related effects were observed on the growth, survival, or reproductive parameters (including testes, prostate and preputial gland weights, sperm count, daily sperm production, or testes histopathology) of male offspring from dams exposed to BPA during gestation and lactation. DES administered in the drinking water at 0. 1 ppm resulted in decreased body weight, body weight change, and food consumption in adult females. In addition, an increase in the duration of gestation and a decrease in the number of pups delivered and number of live pups were also observed in animals exposed to DES. In conclusion, these results do not confirm the previous findings of Sharpe et al. (1996) and show that low doses of BPA had no effects on male sexual development in the rat.

Air Pollutants, Occupational↗

PubMed1999

Toxicity of 3,3',4,4'-tetrachloroazobenzene in rats and mice.

The toxicity of 3,3',4,4'-tetrachloroazobenzene (TCAB) was evaluated in 13-week gavage studies in male and female F344/N rats and B6C3F1 mice. In addition to histopathology, evaluations included clinical chemistry, hematology, thyroid hormone analyses, and reproductive parameters. Groups of 10 rats and 10 mice of each sex were exposed to TCAB at dose levels of 0, 0.1, 1, 3, 10, or 30 mg/kg for 5 days a week for 13 weeks. In the rat studies, the major effects for both males and females included a 10% decrease in terminal body weight at 30 mg/kg/day, an increase in hematopoietic cell proliferation in the spleen at 10 and 30 mg/kg/day, and a responsive anemia at 10 and 30 mg/kg/day. A 15 to 30% decrease in platelet counts and a 20 to 40% decrease in thymus weights was observed at 10 and 30 mg/kg/day. An increase in liver weight up to 15% was found at 3 mg/kg/day and higher doses in males and at 10 and 30 mg/kg/day in females, respectively. An increase in spleen weights up to 15% was observed at 10 and 30 mg/kg/day in males and at 30 mg/kg/day in females. A marked decrease in circulating total thyroxine (TT4) was found in both males and females at all dose levels tested. TT4 could hardly be detected at 10 and 30 mg TCAB/kg/day. In addition, hyperplasia of the forestomach was increased at 3 mg/kg/day and higher doses in males and at 30 mg/kg/day in females. In the mouse studies, an increase in liver and spleen weight was observed up to approximately 25% in both males and females at 10 and 30 mg/kg/day. Hyperplasia of the forestomach was observed at 1 mg/kg/day and higher doses in both males and females. In males, a 30% decrease in thymus weights at 30 mg/kg/day and a 60% decrease in epididymal sperm density at 3 and 30 mg/kg/day was observed. Also in males, centrilobular hypertrophy of hepatocytes and an increase in hematopoietic cell proliferation in the spleen was observed at 3 mg/kg/day and higher doses. Based on the current study and information in the literature, TCAB has dioxin-like properties. Comparison of the effects of TCAB in the present study and in the literature to those with 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) indicates that TCAB is from two to six orders of magnitude less potent than TCDD depending on the end point.

Animals↗

PubMed1988

Cadmium and zinc concentrations in fetal and maternal rat tissue after parenteral administration of cadmium during pregnancy.

Cadmium (Cd) and zinc (Zn) concentrations were determined by solid sampling atomic absorption spectrometry (AAS) in rat maternal and fetal tissues after exposure to cadmium. Cadmium was administered subcutaneously as CdCl2 in saline daily during pregnancy. Two experiments were performed. In expt. I we investigated the tissue concentration at day 19 (gestational age) after administration of several doses: 0, 1.1, 2.2, 4.4, and 8.8 mumol Cd/kg/day. In expt. II the course of the Cd and Zn concentrations during pregnancy was investigated by collecting samples at days 14, 16, 18 and 20, after daily injections of 4.4 mumol Cd/kg. Cadmium concentrations in blood, maternal liver, placenta and fetal liver increased with dose and duration of exposure. Cadmium was heavily accumulated in the liver and transferred to the fetus only in small amounts. The zinc concentration in the maternal liver was positively correlated with the cadmium concentration. In the placenta the zinc concentration was not affected. Zinc in fetal liver was decreased from day 18 onward. Despite relatively high cadmium levels and decreased zinc levels in the fetus, we observed no adverse effects on various reproduction parameters, such as birth weights and obvious malformations.

Animals↗

PubMed1989

Infertility and disease surveillance using a milk recording scheme in the Sahiwal district of Pakistan.

Milk recording was initiated in 1980 in the Sahiwal district of the Punjab province in Pakistan with the aim of identifying superior cattle and buffalo cows. The paper describes how the recording scheme with some modification was utilised to obtain accurate information about production parameters, reproductive traits, blood mineral contents and the prevalence of certain diseases. The main findings indicate that the calving interval in cattle is even higher than previously estimated (22.3 months), that phosphorus and copper deficiency is widespread in the area and that reproductive diseases are not a major factor in infertility. It is concluded that the low reproductive efficiency among cattle and buffaloes in the Sahiwal district is due mainly to phosphorus and copper deficiency accompanied by a low level of feeding and management.

Animals↗

PubMed2001

Developmental toxicity of toluene in male rats: effects on semen quality, testis morphology, and apoptotic neurodegeneration.

In one study, pregnant Wistar rats were exposed to 1200 ppm toluene by inhalation 6 h a day from gestational day (GD) 7 to postnatal day (PND) 18. Sperm analysis was performed in the adult male offspring at PND 110 by using computer-assisted sperm analysis. Toluene did not affect the semen quality of exposed rats. In another study, pregnant rats were exposed to 1800 ppm from GD 7 to GD 20, and the male offspring were killed at PND 11, 21 or 90. Paired testes weight, histopathology and immunoexpression of vimentin in Sertoli cells were used as markers of testis toxicity. In the brain, the number of apoptotic cells in the hippocampus and cerebellum were counted after visualisation by means of the TUNEL assay. Mean body weight in pups of exposed dams was lower than in pups from control litters. This decrease was still statistically significant at PND 11, but at PND 21 and 90 the body weight of toluene-exposed males tended to approach that of the controls. Absolute and relative testes weights were reduced in all three age groups, although not to a statistically significant degree. Histopathological examinations of the testis and immuno-expression of vimentin did not reveal any differences between toluene-exposed animals and control animals. In the hippocampus, almost no apoptosis was observed in any age group, and there were no differences in apoptotic neurodegeneration between male rats exposed to 1800 ppm and control animals at PND 11, 21 or 90. Generally, a marked increase in number of apoptotic cells was observed in cerebellar granule cells at PND 21 compared with the other age groups. Toluene induced a statistically significant increase in the number of apoptotic cells in the cerebellar granule layer at PND 21. The mean was increased from 37 in the control group to 71 in the toluene-exposed group. Thus, the granular cell layer in cerebellum is a highly relevant tissue with which to study toluene-induced apoptosis, because of the continuous migration of neurons and high frequency of neuronal apoptosis during the weaning period. In summary, it is concluded, that neither pre- and postnatal exposure to 1200 ppm toluene nor prenatal exposure to 1800 ppm induced significant effects on the reproductive parameters investigated. However, prenatal exposure to 1800 ppm toluene did increase neuronal apoptosis in the cerebellum of weaned male rats, possibly by delaying postnatal migration of granule cells to their final destination, or by toluene-induced retardation of generalised fetal growth.

Abnormalities, Drug-Induced↗

PubMed2000

Sublethal lead affects pituitary function of rainbow trout during exogenous vitellogenesis.

Sexually maturing female rainbow trout, Oncorhynchus mykiss, were exposed to 10 microg/L of waterborne lead Pb(NO(3))(2) for 12 days during endogenous vitellogenesis and 12 days during exogenous vitellogenesis. Lead had no significant effect on either gonadosomatic indices or mean maximum diameters of developing oocytes during early vitellogenesis. When females were exposed during exogenous vitellogenesis, however, both GSI and oocyte growth were significantly different from controls on day 12. Similarly GSI and oocyte growth was significantly reduced in lead-exposed fish. Atomic absorption spectroscopy measurements of lead levels in liver, ovaries, and blood tissues showed significant levels of lead in the blood. Lead did not accumulate in either the ovaries or the liver. Analysis of pituitary basophils during both endogenous and exogenous vitellogenesis and subsequent comparison with reproductive parameters in the ovaries indicated that GtH-basophils did not significantly increase in controls during endogenous vitellogenesis, and there was no significant change in GSI or ovarian growth in either controls or lead-exposed females. However during exogenous vitellogenesis, control basophils significantly increased over the 12-day experiment, but were not significantly different over 12 days in lead-exposed females. Both GSI and oocyte growth were significantly different from controls in lead-exposed females. The results suggest that naturally occurring changes in GTH-producing basophils during vitellogenesis alters GSI and oocyte growth in female rainbow trout exposed to lead during exogenous vitellogenesis, but not during endogenous vitellogenesis.

Animals↗

PubMed1983

Prevention of cadmium-induced sterility by zinc in the male rat.

The potential of zinc (Zn) to antagonize the adverse effects of cadmium (Cd) on the male reproductive processes was studied. A significant reduction in the weights of the testis and epididymis, the testicular sperm population and oligospermia to azoospermia in the epididymis was recorded in rats treated once s.c. with 2 mg/kg Cd and sacrificed 20 days later. This was accompanied by a significantly reduced serum T and a loss of fertility. Administration of a single s.c. injection of Zn (80 mg/kg) did not alter significantly any of the reproductive parameters studied. On the other hand, Zn given 1/2 to 2 h after Cd resulted in partial recovery. Organ weights and sperm population in these groups were maintained and the fertility rate was 67% and 50% at 5 and 20 days as compared to 67% and 0% at corresponding period in Cd-exposed males. The protective effect diminished when Zn was given more than 2 h after Cd exposure. The most effective regimen of Zn therapy was an administration of a total dose of 80 mg/kg Zn given in 3 injections (15 mg/kg before, 50 mg/kg at the time and 15 mg/kg 2 h after Cd). The results provide evidence that Zn, if given before or within 2 h of Cd exposure, is capable of at least partially reversing its deleterious effects on spermatogenesis, steroidogenesis and fertility of the male rat.

Animals↗

PubMed1986

Exercise reduces gonadal atrophy caused by short photoperiod or blinding of hamsters.

The effect of voluntary exercise upon several reproductive parameters was assessed in male Syrian hamsters. Forty-two animals were caged in five groups and then blinded: Ten housed five per plastic cage; eight housed individually in plastic cages; six housed individually in plastic cages with 15 cm exercise wheels in the cage; eight housed in Wahmann steel activity cages with 36 cm wheels locked to prevent rotation; ten housed in functional Wahmann running wheel cages. At 16 weeks after blinding, animals with access to functional running wheels had significantly larger testes (3.7 +/- 1.0 g) than those with no wheels or locked wheels (1.86 +/- 0.6 g; mean +/- SD; p less than 0.001). These results suggested that voluntary exercise reduces testicular atrophy caused by blinding. A second experiment was run in which the animals were subjected to a short photoperiod (LD 6:18) for 12 weeks instead of blinding. Similar results were obtained except that access to the small exercise wheels did not affect testicular atrophy: Mean testicular mass of animals in individual cages = 0.79 +/- 0.3 g, small wheels = 0.74 +/- 0.4 g, functional Wahmann wheels, 2.56 +/- 1.0 g, locked Wahmann wheels 0.52 +/- 0.1 g (p less than 0.01).

Animals↗