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PubMed1985

Effects of cimetidine, nitrite, cimetidine plus nitrite, and nitrosocimetidine on tumors in mice following transplacental plus chronic lifetime exposure.

Cimetidine (CM), a drug widely prescribed for ulcers, readily undergoes nitrosation to form nitrosocimetidine (NCM), a genotoxic agent. In a test of the chronic effects of NCM in mice, (C57BL/6 X BALB/c)F1 mice were exposed chronically to NCM (113 or 1130 ppm) in the drinking water from preconception through prenatal and neonatal development and adult life. Each group consisted of 40 to 80 mice of each sex, and median survival time was 27 months. Other groups were given CM alone or in combination with NaNO2 (184 or 1840 ppm), or NaNO2 alone. None of the chemical treatments had large effects on reproductive parameters, survival, or incidence of nonneoplastic lesions. CM treatment was associated with a small but significant increase in incidence of lymphomas in females, 41 of 59 (69%), compared with 31 of 66 controls (47%, P = 0.01). No females receiving either dose of NCM developed mammary carcinomas (0 of 91), compared with an incidence of four of 66 controls (6%, P = 0.03). Males given the high-dose combination of CM and NaNO2 showed a higher incidence of lung tumor bearers than controls (71 of 79 versus 30 of 52, P less than 0.01) and also experienced a significant, dose-dependent increase in numbers of large lung tumors (greater than 1 cm in diameter), lung carcinoma, and metastatic lung tumors. Females given the higher dose of NCM had significantly greater incidence of mice with large lung tumors than controls (nine of 41 versus three of 66, P = 0.009). The possibility of carcinogenicity of cimetidine, nitrosocimetidine, and cimetidine plus nitrite is discussed.

Animals↗

PubMed1990

Effect of aluminum on performance and mineral metabolism in young chicks and laying hens.

This study was performed to determine the long-term effects of dietary aluminum on egg production and reproductive parameters in the mature laying hen and on growth rate and feed efficiency in young chicks. The diets used in these studies were adequate in phosphorus and other essential nutrients. Aluminum added to constitute 0.30% of the diet severely depressed growth and reduced feed efficiency, bone ash and plasma phosphorus in male Ross x Leghorn chicks. At the same time, 0.15% added aluminum mildly depressed growth, feed efficiency and bone ash but had no effect on plasma phosphorus levels. The reduction in bone ash was relatively mild, and no clinical signs of rickets were observed. In laying hens, diets containing 0.15% added aluminum did not affect egg production, but 0.30% added aluminum reduced production significantly. Long-term exposure to aluminum increased percent shell in both groups receiving aluminum, whereas egg weight remained similar to that in controls. There were no changes in hatchability or bone ash associated with dietary aluminum. Although dietary aluminum influenced bone aluminum content, egg aluminum content was not affected. These studies indicate that dietary aluminum interferes with systems in addition to phosphorus metabolism.

Aluminum↗

PubMed2005

Programming the offspring of the pig by prenatal social stress: neuroendocrine activity and behaviour.

This study provides evidence in the pig that stress experienced during gestation has long-lasting effects on offspring daughters, including their maternal behaviour. Thirty-six primiparous sows were divided into control and two groups that were stressed (by social mixing) during either the second (Mix 2) or third (Mix 3) trimester of pregnancy. We found detrimental effects of mixing on the mothers' growth, body lesions, and cortisol secretion, but did not observe any significant effects on reproductive parameters including birth weight. At 60 days of age, 48 daughters were randomly selected from the three treatments: half were challenged using a restraint and isolation test. Then, all were culled and brain tissue was collected. In situ hybridisation measurements showed increased expression of CRH mRNA in the PVN in unrestrained Mix 2 and in the amygdala of Mix 2 and Mix 3 daughters. At 67 days, 24 further daughters were mixed to measure their responses to this social stress. All showed increased salivary cortisol secretion, but Mix 2 and Mix 3 daughters showed a greater and longer response than controls. Finally, all 24 were inseminated and at parturition maternal behaviour was measured. Mix 2 and Mix 3 daughters were more restless and more responsive to piglets that approached the head of the sow, traits which previously have been shown to be a component of abnormal maternal behaviour. Indeed, Mix 2 and Mix 3 daughters also tended to bite at their piglets more than control daughters.

Animals↗

PubMed1992

Effects of methoxychlor treatment of pregnant mice on female offspring of the treated and subsequent pregnancies.

This study was designed to assess whether exposure to the estrogenic pesticide methoxychlor (MXC) during pregnancy would affect reproductive parameters not only in female offspring exposed prenatally, but also in those of a subsequent litter. Mice were exposed via oral gavage to 7.5, 5.0, or 2.5 mg technical grade MXC (50%) or 0.025 mg estradiol-17 beta (E-17 beta) from days 6 to 15 of pregnancy. Following delivery, female offspring (F1a) were cross-fostered and sacrificed at 8 weeks of age. Mothers exposed during their first pregnancy were allowed to mate again and their second set of offspring (F1b) were similarly evaluated to detect any latent effects from the initial exposure. Mice exposed to 7.5 mg MXC were unable to carry their litters to term. Results revealed a significant increase in the length of gestation of mice exposed to both E-17 beta and 5.0 mg MXC. A larger percentage of atretic follicles appeared in the ovaries of F1a females exposed prenatally to 5.0 mg MXC when compared to controls. Females from the F1b litter displayed a significant advance in time of vaginal opening, an apparent residual effect of MXC from a mother exposed during a previous pregnancy.

Abnormalities, Drug-Induced↗

PubMed1996

Nonclinical toxicology studies with zidovudine: reproductive toxicity studies in rats and rabbits.

Zidovudine (ZDV) was evaluated for adverse effects on reproduction and fetal development in animal test species. Standard preclinical tests for reproduction and fertility, developmental toxicity, and postnatal toxicity were conducted in CD (Sprague-Dawley) rats and a developmental toxicity study was conducted in New Zealand white rabbits. In an additional study, reproductive outcome was characterized in female rats given ZDV before, during, or after mating and drug levels in the plasma and milk of lactating rats were determined. Finally, drug exposure data including observed peak plasma concentrations (Cmax) and area under the concentration-time curve (AUC) were evaluated for pregnant rats and rabbits. In a reproduction/fertility study in CD rats, toxicity to the early rat embryo, manifested as an increase in early resorptions and a decrease in litter size, was noted following dosage of the parental animals with 75 or 225 mg ZDV/kg bid. A dose of 25 mg/kg bid was a no-effect level in rats. At the time of mating, male rats had been dosed for 85 days, and females had been dosed for 26 days. To further evaluate the effects of ZDV on reproduction, dosing of male rats was continued to 149 days when they were mated a second time to virgin, untreated females. All reproductive parameters were normal in the untreated females from this second mating, indicating that the embryotoxic effect of the drug was not likely mediated by a genotoxic or other effect in the male. A separate study in female CD rats given 225 mg/kg bid for various periods pre- or postconception suggests that the toxic effect of ZDV is primarily to the early rodent embryo. Early embryo death did not occur in rats or rabbits in standard developmental (teratology) studies; however, pregnant New Zealand white rabbits given 250 mg/kg bid during gestation Days 6-18 showed reduced weight gain, anemia, and an increase in late fetal deaths. No other evidence of developmental toxicity was noted in either species, and ZDV was not teratogenic in rats or rabbits given up to 250 mg/kg bid during the period of major organogenesis. At this dose, Cmax values in rats and rabbits were approximately 234 and 150 times higher, respectively, than the mean steady-state serum concentration in adults following chronic oral administration of 250 mg every 4 hr. In both the reproduction/fertility study and a peri- and postnatal study in rats, liveborn offspring showed no adverse effects on survival, growth, or developmental measurements.

Animals↗

PubMed1988

Morphological and genetic characteristics of the open-eyelid mutant spontaneously occurring in NC-strain mice.

A heritable open-eyelid mutant which arose spontaneously in the NC strain of mouse in 1982 has been maintained as the NC-eob line through brother-sister matings. When the line exceeded the 12th generation, its reproductive capabilities were initially compared with those of the NC strain. Then eye abnormalities were investigated morphologically and genetically. Although most of the reproductive parameters in the NC-eob line were comparable to those in the NC strain, a significant decrease was observed in the mean number of pups delivered, and the viability of pups at 7 days of age was reduced to 55%. The eyelids of pups were widely open at birth. The exposed cornea dried within a few hours and a bloody exudate appeared around the margin of the eyelids. At 1 day of age, the eye opening was smaller in size and covered with a scab. Histological examination demonstrated apparent inflammatory changes in the cornea and conjunctiva. At 21 days of age, the eyes revealed opacity, a rough surface, and microphthalmia. Histological findings in the cornea, such as keratosis and vascularization, coincided with the eye opacity. The weight and size of the eyeballs were almost the same as those in normal NC pups. However, a significant decrease in the length of the palpebral rima was evident and this was considered to be the cause of the microphthalmia. The results of genetic analysis indicated that these eye abnormalities were caused by an autosomal recessive gene, eob. These results suggested that the eob gene might be a new mutation manifesting semi-lethality as a pleiotropic effect.

Animals↗

PubMed2006

Multiscale approach of fish responses to different types of environmental contaminations: a case study.

In order to study the responses of wild fish to environmental contaminations, different sites (two references and three contaminated) were sampled across the Walloon hydrographical network (southern Belgium). The status of fish communities was characterized according to an index of biotic integrity (IBI). Furthermore, population structure, reproductive parameters and biochemical assays were performed on chub (Leuciscus cephalus) as sentinel species. The results showed impaired responses in fish sampled downstream paper mill effluents (BKME), in a polychlorinated biphenyls (PCB) contaminated site, and in a river receiving pesticides (i.e. atrazine and hexachlorocyclohexane). High level of hepatic 7-ethoxyresorufin-Odeethylase (EROD) activity were evidence of direct toxicant exposure, while population structures showed unbalanced size-frequency distributions. Moreover, in the pesticide contaminated site, a higher proportion of atretic oocytes was found in females and abnormally high plasma alkali-labile phosphorus (ALP) values were noticed in males, compared to reference sites, suggesting that chubs were exposed to estrogenic compounds. IBI scores from both sites were also lower than in reference sites. On the other hand, no particular response was found in hepatic glutathione-S-transferase (GST) activities, hepatic heat-shock protein HSP70 concentrations and plasma sex steroids (estradiol-17beta, 11-ketotestosterone and testosterone) in chubs from any sites. By using a multiparametric approach, a better understanding of response mechanisms to pollution in fish may be achieved in order to improve the ecological status of river ecosystems.

Analysis of Variance↗

PubMed2006

Reproductive effects of heavy metal accumulation on breeding feral pigeons (Columba livia).

To investigate the effects of heavy metal accumulations on breeding birds, we compared the egg size, eggshell thickness and some reproductive parameters in feral pigeon populations collected from Seoul and Ansan colonies. The results showed that concentrations of Pb in bone and Cd in kidney of adult pigeons in Seoul were three times higher than in Ansan colony. Significant positive correlation was also observed between Pb and Zn in bone and Cd and Zn in kidney of adult pigeons from Seoul, but not Ansan. This indicates that pigeons at Seoul may be affected more by the toxic Pb and Cd exposure in the environment rather than those at Ansan because of the antagonistic action of Zn against Pb and Cd toxicity. No significant difference was observed in egg characteristics (egg length, width and shell thickness), clutch size (number of eggs per clutch), incubation periods and hatchability of squabs between the two study sites. Although no significant difference was observed, body weight, and primary wing, bill and tarsus lengths of nestlings from Seoul which is more polluted were rather smaller than those from Ansan. Nestlings at Seoul fledged significantly later than at the less polluted site (Ansan). We also observed significantly lower fledging success at Seoul than Ansan colony. Elevated metal exposure may thus result in decreasing growth rate in pigeon nestlings resulting in fledging length and fledging success. Our results suggest a possible effect of heavy metal bioaccumulation on breeding of feral pigeons.

Animals↗

PubMed1983

The effect of ambient temperature and energy level on reproduction in Red-Legged partridges.

The effects of temperature and dietary energy on various reproductive parameters were studied in Red-Legged partridges (Alectoris graeca) reared in three environmental chambers at either 18.3, 23.9, or 29.5 C. These birds were then cycled through two consecutive production periods. In Period 1, at 38 weeks of age, the birds in each chamber, 118 pair total, were divided into four subgroups and fed a diet containing either 2600, 2800, 3000, or 3200 kcal/kg of metabolizable energy. The energy to protein ratio was held constant at 186. In Period 2, at 63 weeks of age, chambers with the lowest and highest temperatures were changed from 18.3 to 15.6 C and 29.5 to 32.2 C, respectively. Only the lowest and highest energy diets were used. In both periods, the birds kept at higher temperatures and fed the high energy diets consumed significantly less feed (P less than .05) than the other comparable groups. Hatchability was significantly higher (P less than .05) in groups fed the 3000 and 3200 kcal/kg diets as compared to the 2600 kcal/kg diet group. In Period 2, egg production increased in all groups, but birds kept at 32.2 C laid significantly fewer (P less than .05) eggs per bird than those kept at 15.6 and 23.9 C, respectively. The best performance, as measured by salable chicks produced per hen, was obtained in the group kept under a constant temperature of 23.9 C and fed the high energy diet (3200 kcal/kg).

Animals↗

PubMed2000

The effects of prophylactic anthelmintic treatment on the productivity of traditionally managed Djallonke sheep and West African Dwarf goats kept under high trypanosomosis risk.

The effects of a prophylactic anthelmintic intervention on the productivity of village based sheep and goats was studied in an area of high trypanosomosis risk in The Gambia during 2 and 3 years, respectively. In total, 223 sheep and 385 goats from five villages were included. Allocation to treatment groups (treated-control) was randomised by village, based on age and sex. Three treatments per rainy season were applied with Fenbendazole (Panacur, Hoechst, 2.5%, 5 mg/kg). Mean nematode egg excretion per gram faeces (EPG) of the treated groups were significantly reduced by prophylactic anthelmintic treatment, indicating the efficiency of the treatment despite the risk of rapid reinfestation. Weight gain benefits of anthelmintic treatment were observed in all age categories (> 6 month) of sheep but not in goats. Kidding rates were significantly increased whilst the same positive trends were observed for other reproductive parameters (litter size, parturition interval) in both goats and sheep without reaching statistical significance. Birth weights of offspring born out of treated does and ewes were higher (P < 0.05) than those from the controls. In contrast, growth rates until 3 months of age were not influenced by the treatment status of the dam. Mortality rates until the age of 3 months of kids from treated does were significantly lower than of those from control does. Mean Packed Red Cell Volume (PCV) levels during the rains were significantly higher in treated goats than in control goats. The same trend was observed in sheep. In general, there were no interactions between trypanosome infections and effect of anthelmintic treatment, thus both factors acted independently. Finally, the live weight productivity index (12 months old-offspring in kg/year per dam) for treated dams was 24% and 47% higher than in control ewes and does, respectively. It can be concluded that, despite the continuous risk of trypanosome infections which has a negative impact on their productivity, a beneficial effect of anthelmintic treatment was observed in both species but most obviously in goats, measured as an increased production and improved health status. A cost-benefit analysis should be carried out in order to confirm whether prophylactic anthelmintic treatment can be recommended to farmers to increase their income from small ruminant production. Nevertheless, anthelmintic treatment will certainly optimise the trypanotolerance in these breeds.

Animals↗

PubMed1985

Effects of vitamin A and beta-carotene on reproductive performance in gilts.

The effects of vitamin A and beta-carotene on various reproductive parameters were examined in 108 crossbred gilts. Gilts were fed a diet free of vitamin A and beta-carotene for 5 wk, then assigned to one of eight treatments. Statistical comparisons were performed on three sub-groupings of these treatments as follows: (1) DEFICIENT (received 2,100 IU of vitamin A X head-1 X d-1, (2) FED (received dietary supplementation of 0, 2,100 or 12,300 IU vitamin A and (or) 0, 32.6 or 65.2 mg beta-carotene X head-1 X d-1) or (3) INJECTED (received injection supplementation of 0 or 12,300 IU vitamin A and 32.6 mg beta-carotene X head-1 X d-1, administered once weekly). Gilts remained on treatment through weaning of litters at 21 d postpartum. Plasma vitamin A and beta-carotene levels were greatly elevated in INJECTED gilts. Concentrations of these compounds in plasma were similar between DEFICIENT and FED gilts. There was no treatment difference in number of corpora lutea/gilt. Embryonic mortality was lowest (P less than .01 to .02) in INJECTED gilts (14 +/- 3%) compared with DEFICIENT (29 +/- 5%) or FED (25 +/- 3%) gilts. Baby pig mortality averaged 6 +/- 1% and was not different among treatments. INJECTED gilts had more (P less than .05 to .01) piglets/litter at birth and at weaning (9.5 +/- .3 and 9.0 +/- .3 piglets/litter, respectively) than DEFICIENT (7.9 +/- .5 and 7.6 +/- .5 piglets/litter) or FED gilts (8.7 +/- .3 and 8.1 +/- .3 piglets/litter).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

The selective estrogen receptor modulator, raloxifene: segment II studies in rats and rabbits.

Raloxifene is a nonsteroidal, selective estrogen receptor modulator developed by Eli Lilly and Company primarily as a therapeutic agent for postmenopausal osteoporosis. Two Segment II studies were conducted that examined maternal reproductive parameters and fetal outcome following gestational exposure to raloxifene. Pregnant CD rats (25/group) and New Zealand white rabbits (20/group) were dosed once daily by oral gavage with 0, 0.1, 1, or 10 mg/kg on Gestation Days (GD) 6 through 17 and 7 through 19, respectively. Maternal body weight and food consumption were monitored throughout pregnancy. Caesarean sections were performed on GD 20 and GD 28 for rats and rabbits, respectively, to evaluate fetal viability, weight, and morphology. In rats, maternal body weight, body weight gain, and food consumption were reduced in all raloxifene treatment groups. Fetal viability was depressed in the 10-mg/kg group and was often associated with signs of hemorrhaging from the vagina. Fetal growth retardation was indicated in the 1- and/or 10-mg/kg groups by increased incidences of fetal runts and the developmental deviations, wavy ribs and kidney cavitation. There was no evidence of treatment-related malformations in rat fetuses. In rabbits, depressions in body weight gain and food consumption occurred in the 10-mg/kg group, and a single abortion occurred in the 1-mg/kg group. Fetal viability and weights were not affected in any of the raloxifene treatment groups. The overall proportions of fetuses with malformations, deviations, or variations were not affected by treatment with raloxifene; however, one fetus each from the 0.1-, 1-, and 10-mg/kg groups had incomplete closure of the interventricular septum. Therefore, maternal and fetal no-effect levels were not obtained in this study of raloxifene.

Administration, Oral↗

PubMed2000

Dosing via gavage or diet for reproduction studies: a pilot study using two fat-soluble compounds-hexachlorobenzene and aroclor 1254.

The choice of a dosing route for in vivo toxicological tests is often dictated by practical constraints. Reproduction studies are particularly challenging in this regard since the determination of no-effect levels and allowable daily intakes from reproduction data encompasses exposure of the dam to the test xenobiotic prior to pregnancy, during gestation and during lactation. The fetus/infant can be exposed to the xenobiotic as well as the dam's metabolic products of the test xenobiotic during gestation and lactation. We initiated a series of two-litter, pilot reproduction studies with Sprague-Dawley and Fischer 344 rats to specifically ascertain the amount of xenobiotic and its metabolites ingested by the nursing neonate on lactation days 4, 7, 12, 17 and 21, when its dam received the xenobiotic via its diet or by gavage. The xenobiotics studied in this initial series of experiments were hexachlorobenzene (HCB) and Aroclor(R) 1254 (polychlorinated biphenyls; PCBs). The dams were dosed for 28 days, mated to untreated males and then remated approximately 2 weeks after weaning their first litter to a second untreated male. Dietary levels of 10 ppm HCB or 10 ppm PCBs, and gavage doses of 0.9 mg HCB or 0.8 mg PCBs/kg body weight/day were chosen and resulted in similar doses of HCB and PCBs per unit of the body weight of the dam during the premating period. There were no apparent toxicological effects regarding the dam nor were any of the reproduction parameters (feed consumption, dam weight, litter size, pup weight, external anomalies and day 4 viability index) significantly different from control values. Following impregnation, the body weight of the dam increased appreciably during gestation, but its feed consumption increased only slightly. During lactation, the dam's feed consumption increased markedly while its body weight increased slightly. Consequently, when dams received the xenobiotic in their diet they consumed slightly less xenobiotic per unit of body weight during gestation when compared to the gavaged dams, whereas the situation was dramatically reversed during lactation. While the greater consumption of xenobiotic by the dietary-dosed dams during lactation did result in more HCB (P</=0.0001 for both litters) and PCBs/metabolites (litter one: P=0.05; litter two: P</=0.0001) in the suckling neonate's stomach contents in both generations, there was no evidence of any differences between the two litters when each sampling date was assessed separately, except for the day 4-HCB results when the litter one pups had more HCB in their stomachs (P=0.018). For the PCBs, the F344 neonates were found to have more PCBs in their stomachs (litter one P=0.0015; litter two P=0.002) than the Sprague-Dawley neonates. In addition, the amount of HCB, PCBs and fat in the neonates' stomachs decreased during lactation, as the pups age increased (P</=0.035). These preliminary results suggest that analogous amounts of HCB and PCBs given via diet or gavage may not result in similar lactational exposure by the suckling neonate.

Animals↗

PubMed1997

Estrus, fertility, early embryo development, and autologous embryo transfer in laboratory woodchucks (Marmota monax).

Reproductive parameters were studied in female laboratory woodchucks over a 6-year period. The pregnancy rate in adult females after ad libitum exposure to a male (n = 643) was 72%; that after limited (4 to 8 h) exposure with video observations (n = 31) was only 37%. However, limited exposure resulted in a 75% ovulation rate, suggesting a problem with fertilization and not ovulation. The ovulation rate was 0% in the absence of mating (n = 10), suggesting that spontaneous ovulation is not the usual situation in this species. With ad libitum mating, fertility was greater (P < 0.05) for 2- to 4-year-old females (73%) than for 1-year-old (56%) or > or = 5-year-old (58%) females. Mean (+/-SEM) litter size at birth was greater (P < 0.05) for 2- to 5-year-old animals (4.0 +/- 0.1) than for 1-year-old animals (2.9 +/- 0.2). However, in 1-year-old females the neonatal mortality was low, and the litter size at weaning (2.4 +/- 0.3 pups) did not differ from that of older females (2.7 +/- 0.1 pups). The measurement of vulval diameter every 3 to 4 days in 31 adult females suggested that enlargement to > or = 7 mm was indicative of proestrus or estrus and was a good indicator of willingness to accept mounting by males. Vulval swelling > or = 7 mm (n = 31) lasted 5 to 47 days. Fertile mating occurred from 3 to 30 days after vulval diameter reached > or = 7 mm, near the time of peak enlargement (10.1 +/- 0.2 mm), and was followed in several days by a decrease in vulval size. Fifty-three females were allowed only limited (6 to 10 h) video-observed exposure to males, with (n = 26) or without (n = 27) another 12 to 24 h of unobserved exposure, and were examined surgically for ovulation and pregnancy at known times after mating. There were no consistent differences among nonovulating, ovulating nonfertile, and fertile females in the longest duration of mating (7.2 +/- 0.4 min) or in the number of matings lasting > or = 1 min (5.7 +/- 0.8). Compared with nonfertile females, fertile females experienced more matings > or = 3 min in duration (3.3 +/- 0.4 versus 1.8 +/- 0.2) and > or = 5 min in duration (2.9 +/- 0.4 versus 1.1 +/- 0.1). At postmating days 1, 2, 3, 4, 5, 6, and 7 the embryos were observed to be 1-, 4-, 4- to 32-cell morulae, 16- to 60-cell morulae, free-floating blastocysts, anti-measometrial peri-implantation blastocysts, and attached blastocysts respectively. Autologous transfer of day-5 uterine embryos of normal appearance into the noncontiguous contralateral uterine horn was performed in five females that had been subjected to a hemi-ovariectomy. Transfers resulted in pregnancy and litters in four of the five females. The results suggest that this large, circannual sciurid rodent can be successfully and predictably bred as a laboratory animal model, has vulval changes indicative of proestrus, is principally an induced ovulator, has an early embryo development rate similar to that of rats and mice, and may be amenable to reproductive technologies developed for more common laboratory rodents.

Animals↗

PubMed2000

Developmental toxicity of 1,6-hexamethylene diisocyanate (HDI) in the Sprague-Dawley rat.

BACKGROUND: 1,6-Hexamethylene diisocyanate (HDI), a widely used chemical in commercial polyurethane manufacture, has been shown to affect the respiratory tract of experimental animals. However, its potential to affect neonatal development, particularly after inhalation exposure, is less well described. The present study was conducted to assess the developmental toxicity of HDI. METHODS: Gravid Sprague-Dawley rats were exposed to concentrations of 0, 0. 005, 0.050, or 0.300 ppm HDI via inhalation (whole-body exposure) on days 0-19 of gestation. Maternal toxicity, as demonstrated by clinical signs and changes in body weight gain during gestation, was characterized. Dams were sacrificed on gestation day 20, at which time fetuses were removed by cesarean section, the uterus was examined, and a gross maternal necropsy was performed. Maternal evaluation also included lung weight and a detailed histopathologic assessment of the nasal turbinates, larynx, trachea, and lungs. All fetuses were evaluated for external anomalies. Approximately one-half of each litter was examined for visceral effects, the other half underwent a skeletal (bone and cartilage) examination. RESULTS: Maternal toxicity was demonstrated in the 0.300- and, to a lesser extent, in the 0.050-ppm exposure groups. No maternal effects were noted in the 0.005-ppm group. Test compound-related maternal effects were restricted to histopathological findings and included acanthosis, hyperkeratosis, inflammation of the nasal turbinates, and, more seriously, degeneration of the olfactory epithelium. No pathological alterations were noted in the larynx, trachea, or lungs in any dose group. No test compound-related effects were observed on any reproductive parameters, or any embryonic endpoints, including pre/postimplantation loss and resorption. There were no effects on litter size or the number of fetuses per implantation site and no effects on fetal or placental weights were observed. No test compound-related fetal external, visceral, or skeletal findings were observed. No effect on the fetal or litter incidence of total malformations or variations was observed, and there was no difference in the incidence of malformations between males and females. CONCLUSIONS: Administered as described in this study, 1, 6-HDI produced maternal effects (nasal turbinate histopathology) at concentrations of 0.050 and 0.300 ppm with no developmental toxicity observed at any concentration.

Abnormalities, Drug-Induced↗

PubMed1980

Perinatal study in Tientsin: 1978.

Clinical records of a total of 3320 singleton births, representing the year 1978, at the two Tientsin Medical College Hospitals, Tientsin, People's Republic of China, were studied to ascertain (a) reproductive parameters such as the average age of the mothers at first and successive births and (b) the relationships between perinatal deaths, prematurity and birth weight and the mothers's age, number of previous pregnancies, parity, maternal conditions in the prenatal and delivery period and operative procedures of delivery.

Adult↗

PubMedDate not supplied

Time-dependent effects of lead on rat reproductive functions.

The effects of exposure to lead on endocrine function and the reproductive parameters were studied in pubertal rats treated with 1.0 g l-1 lead acetate in drinking water for 20 days (subacute group) or 9 months (chronic group) in addition to i.v. injections of lead acetate (0.1 mg 100 g-1 body wt.) every 10 (subacute group) or 15 days (chronic group). Although basal levels of testosterone were higher both in plasma and in testes of acutely intoxicated animals, the circulating levels of luteinizing hormone (LH) were not affected in either group, nor was the LH-releasing hormone content of the median eminence. The density of [125I]LH/human chorionic gonadotrophin (hCG) binding sites in testicular homogenates was reduced by saturnism in both groups, concomitant with a significantly increased apparent affinity constant of the hormone-receptor complex. These data can be viewed as the result of a mixture of specific lead toxicity (e.g. at the enzyme level) with other more general actions (e.g. at the level of the hypothalamus-pituitary-testicular axis).

Animals↗

PubMed2007

Heat stress-induced apoptosis in porcine in vitro fertilized and parthenogenetic preimplantation-stage embryos.

Decades worth of research have consistently shown the adverse effects of elevated temperatures on reproductive parameters of livestock species. The objective of this study was to evaluate the developmental and apoptotic responses of porcine in vitro fertilized (IVF) and parthenogenetically activated (PA) embryos heat stressed at the late 1-cell stage. Embryos were heat stressed (HS) at 42 degrees C for 9 hr starting 22 hr after insemination or artificial activation stimulus. Non heat-stressed (NHS) control embryos were maintained at 39 degrees C for the duration of the experiments. TUNEL staining on Day 5 of development demonstrated that heat stress elicited a significant apoptotic response in IVF embryos (45.6% of HS embryos and 26.7% of NHS embryos were apoptotic; P<0.05), but not in PA embryos (51.1% and 39.9% for HS and NHS embryos, respectively; P>0.1). And, while IVF embryos were highly susceptible to heat-induced developmental perturbations (20.6% and 8.8% development to blastocyst for NHS and HS embryos, respectively; P<0.05), elevated temperatures did not affect blastocyst rates in PA embryos (22.2% for NHS PA embryos and 21.2% for HS PA embryos; P>0.1). These findings indicate that, as in other systems studied, IVF pig embryos are directly affected adversely by heat stress conditions. Parthenogenetic embryos, though, appear to be surprisingly tolerant of the elevated temperatures. The differences between IVF and PA embryos in their response to heat stress warrants further investigation.

Animals↗