Body Weight Gain Of Dams Research Articles

Embryo toxicity of pefloxacin in mice

Fluoroquinolones are extremely useful agents and an important therapeutic advance. Each fluoroquinolones tends produce characteristic adverse effects. Different studies showed that there was evidence about adverse effects of some :fluoroquinolones as levofloxacin, alatrofloxacin, trovaflxacin and moxifloxacin on the pregnant experimental lab. Animals when they were administered higher than the maximum recommended human doses , the current study was conducted to highlight the effects of different dosages of pefloxacin on the pregnant mice .The study revealed that the litter size and weight of bi1th were unaffected at the recommended oral human doses. Also reflects that there were little effects on body weight gain of dams when the dose exceeds the maximum recommended human dosage. No teratogenic effects were observed even at high oral doses. This project needs further investigation using different lab. Animals with large sample size.

Ethanolic Extract of Pluchea indica Less leaf Increases Serum Growth Hormone in Lactating Rats

The objectives of the study were to evaluate the effect of ethanolic extract of P. indica Less leaf (EPI) on serum growth hormone (GH), milk yield, body weight gain of dams, and dam’s organ weight in lactating rats. A total of 25 lactating rats with six pups were randomized and distributed to one of five treatments (control (RO water), standard (domperidone 2,5 mg/kg BW/day), EPI 250 (250 mg/kg BW of EPI), EPI 500 (500 mg/kg BW of EPI), and EPI 750 (750 mg/kg BW of EPI)). The treatment was administered daily starting from the 2nd until the 15th day of lactation. On the 16th day serum growth hormone level, body and organ weight of rats were measured. Serum GH levels in the EPI 750 group (1963.25 ± 360.91 pg/µL) increased significantly compared to the domperidone (409.46 ± 28.80 pg/µL) and the control group (723.40 ± 95.78 pg/µL, p0.05). There was significant body weight gain in the EPI 750 group compared with the domperidone group. There was no significant difference in organ weight gain in each group. The study revealed that ethanolic extract of P. indica Less leaf can increase serum growth hormone in lactating rats.

Perinatal free-choice of a high-calorie low-protein diet affects leptin signaling through IRS1 and AMPK dephosphorylation in the hypothalami of female rat offspring in adulthood.

We aimed to investigate whether a dysregulated maternal diet during gestation and lactation induces long-lasting changes in the hypothalamic control of feeding behavior in the offspring and whether this effect is sex specific. The study included an analysis of appetite-regulating metabolic hormones and hypothalamic signaling in male and female offspring in adulthood after exposure to a free-choice high-calorie palatable low-protein (P) diet or standard chow (C) during (pre)gestation/lactation (maternal) and/or postweaning (offspring). Maternal exposure to the P diet resulted in decreased protein intake and body weight gain in dams and decreased body weight gain in offspring during lactation. The maternal P diet (PC) specifically increased feed efficacy and decreased body weight and cholesterol levels in the female offspring in adulthood, but no changes in adiposity or leptin levels were found. In contrast, P diet exposure after weaning (CP and PP) increased caloric intake, adiposity and circulating levels of leptin in the male and female offspring in adulthood. The hypothalami of the female offspring exposed to the maternal P diet (PC and PP) expressed high levels of the phospho-leptin receptor and low levels of SOCS3, phospho-IRS1 and phospho-AMPK, regardless of the postweaning diet. The hypothalami of the female rats in the PC group also showed increased levels of STAT3 and the orexigenic neuropeptide Agrp. Maternal exposure to a free-choice high-calorie low-protein diet induces a long-term feed efficacy associated with changes in leptin signaling through IRS-1 and AMPK dephosphorylation in the hypothalami of female offspring in adulthood.

Impact of Using Yeast as Feed Additive on Production Performance and Immune Responses of She-Camels and Their Newborn Calves during Peri-Parturation Period

She-camels face down-regulation of immune responses during pregnancy that may lead to viral and bacterial infections so increases the dangers affecting their newborn calves. This study aimed to improve the body weight and immune responses of she-camels and their newborn calves. A total of 10 dams were divided into two equal groups; G1 (fed the basal diet only) and G2 (fed the basal diet & Saccharomyces cerevisiae (SC); 0.5 g/head/day). Dams' and calves' plasma, milk samples were collected. Quantitative analysis of IgG, IgA & IFN-γ levels in samples was done by ELISA and Body weights were recorded monthly. Results revealed significant increases (P<0.05) in body weight, body weight gain of dams and calves' birth weight in G2 compared to G1. IgG2 levels dams were higher than IgG1 at all durations, IgA levels didn't show any significant change in groups while IFN-γ showed an increased level in G2 more than G1 from the time of calving to one month post calving. IgG, IgA & IFN-γ levels in milk didn't show significant differences between the experimental groups. Calves' IgG in G2 showed higher significant levels compared to G1 from birth to one month after birth, IgA & IFN-γ levels in G2 showed significant increase at one month after birth. Conclusion: SC is a good feed additive for she-camels during peri-partum. It improved total body weight, body weight gain and birth weight of calves. Immune responses of dams and calves were enhanced that may help in facing the stressful pregnancy event.

IMPACT OF USING YEAST AS FEED ADDITIVE ON PRODUCTION PERFORMANCE AND IMMUNE RESPONSES OF SHE-CAMELS AND THEIR NEWBORN CALVES DURING PERI-PARTURATION PERIOD

She-camels face down-regulation of immune responses during pregnancy that may lead to viral and bacterial infections so increases the dangers affecting their newborn calves. This study aimed to improve the body weight and immune responses of she-camels and their newborn calves. A total of 10 dams were divided into two equal groups; G1 (fed the basal diet only) and G2 (fed the basal diet & Saccharomyces cerevisiae (SC); 0.5 g/head/day). Dams' and calves' plasma, milk samples were collected. Quantitative analysis of IgG, IgA & IFN-γ levels in samples was done by ELISA and Body weights were recorded monthly. Results revealed significant increases (P<0.05) in body weight, body weight gain of dams and calves' birth weight in G2 compared to G1. IgG2 levels dams were higher than IgG1 at all durations, IgA levels didn't show any significant change in groups while IFN-γ showed an increased level in G2 more than G1 from the time of calving to one month post calving. IgG, IgA & IFN-γ levels in milk didn't show significant differences between the experimental groups. Calves' IgG in G2 showed higher significant levels compared to G1 from birth to one month after birth, IgA & IFN-γ levels in G2 showed significant increase at one month after birth. Conclusion: SC is a good feed additive for she-camels during peri-partum. It improved total body weight, body weight gain and birth weight of calves. Immune responses of dams and calves were enhanced that may help in facing the stressful pregnancy event.

Protective Effect of Olive Oil against Teratogenecity Induced by Mancozeb in Albino Rats

Aim: this study aimed to investigate the protective effect of extra-virgin olive oil (EVOO) against teratogenicity of the fungicide mancozeb. Methods: after pregnancy confirmation, 32 pregnant rats were divided into 4-groups (n=8). The 1st group orally administered tap water (-ve control), the 2nd group (+ve control) was administered EVOO (0.5ml/dam) from the1st to 20th day of pregnancy. The 3rd and the 4th groups were administered 200 mg/kg mancozeb during the period of organogenesis, from the 6th to 15th day of pregnancy. The 4th group received the mentioned dose of EVOO prior to the pesticide administration. Cesarean section was performed on day 20 of pregnancy and the maternal and fetal parameters were recorded. Results: mancozeb induced maternal toxicity manifested as lower body weight gain of dams, increased number of late resorption sites/litter in comparison with the control group and mancozeb group pretreated with EVOO. Mancozeb evoked a decrease in fetal body weight, altered sex ratio (M/F) as well as increased incidence of fetal external, visceral and skeletal abnormalities. Treatment with virgin oil reduced the congenital malformations. Conclusively, the present study elucidates the protective role of EVOO as a result of antioxidant activity which scavenges the reactive oxygen species which induced cytotoxicity and increased prenatal mortalities.

Neurobehavioral toxicity in progeny of rat mothers exposed to methylmercury during gestation.

Methylmercury (MeHg) is recognized as one of the most hazardous environmental pollutants. This may be a concern to long-term consumption of contaminated fish and seafood for health risk to pregnant women and their children. An animal study was conducted to assess the effect of MeHg exposure on rodent offspring following in utero exposure. Pregnant Wister rats were treated by gavage with MeHg at dose levels of 0.5, 1.0 and 2.0 mg/kg/day from gestation day (GD) 5 till parturition, and then were allowed to deliver. Dams treated with 2.0 mg/kg/day MeHg group showed signs of toxicity such as gait alterations and hyperactivity resulting in the failure to deliver sustainable viable pups. MeHg had significant effects on body weight gain of dams during GD 5 till parturition. MeHg had no significant effects on the ages of physical developments such as pinna detachment, incisor eruptions or eye opening as well as alter cliff avoidance, surface righting, swimming ontogeny, startle reflex, pivoting, negative geotaxis, or forelimb and hindlimb grip strength in either sex. Exposure to 1.0 mg/kg/day MeHg treatment group prolonged gestation period, retard mid-air righting in male pups, shortened forelimb grip strength measured on rotating rod in either sex and enhanced open field behaviour in male pups. Data obtained from Functional Observation Battery (FOB) also revealed impairment of neuromotor performance in male pups. The male pups appeared to be more susceptible than the female pups. Overall, the dose level of MeHg in the present study produced a few adverse effects on the neurobehavioral parameters, and it may alter neuromotor performance of the male pups.

Effects of early gestational all- trans retinoic acid treatment on motor skills: A longitudinal study in the offspring of Sprague–Dawley rats

The purpose of the present study was to investigate the behavioral outcomes of all- trans retinoic acid (RA) treatment in the period spanning gestational day (GD) 8–10. A sublethal dose (2.5 mg/kg b.w.) compatible with high neonatal survival, sufficient to supply male offspring for later behavioral testing, was used. Indeed, the mortality rate at birth was 7.8%. Reproduction parameters (body weight gain of dams during gestation, number of dams giving birth, pregnancy length, litter size at birth), offspring body weight gain and the development of their somatic characteristics (ear unfolding, auditory conduit opening, eyes opening, hair growth) were not altered by RA. Instead, the onset of righting reflex and negative geotaxis were delayed by 2 days, suggesting vestibular involvement and abnormal functioning of the cerebellum. Then, the performance of RA-treated rats on open field and rotarod/accelerod tasks was assessed from postnatal day (PND) 21 to 90. Similar to the previously investigated GD 11–13 RA treatment, the GD 8–10 RA treatment impaired the open field activity and rotarod/accelerod performance in young adult rats, thus suggesting a task-specific rather than a stage-specific effect of low-dose retinoids during brain development. The delayed appearance of these outcomes underlines the relevance of longitudinal studies to sort out specific RA-targeted neurochemical-behavioral pathways that could be labelled as having no phenotype based on standard examination at birth.

Effects of separate and combined exposure to the pesticides methamidophos and chlorothalonil on the development of suckling rats

It has been suggested that, in some cases, exposure to environmental contaminants affects children more profoundly than adults. It is important to evaluate adverse health outcomes in children, a population susceptible to toxic chemicals and mixtures. We examined the effects that maternal exposure to two pesticides had on maturational aspects of offspring development during the nursing period. Nursing female rats were exposed to 1–4 mg/kg of intraperitoneal methamidophos, 200–800 mg/kg of chlorothalonil, or both. The higher doses of methamidophos affected pup viability by day 21 of life. Both pesticides, alone or together, affected body weight gain of dams and offspring. Developmental milestones evaluated in the pups were incisor eruption, ear unfolding, eye opening and testis descent. Although no clear dose–response relationship was established between these milestones and exposure to methamidophos or chlorothalonil, incisor eruption was accelerated in many groups, and the majority of rat offspring exposed to methamidophos presented later ear unfolding and eye opening than did the control group offspring. Sexual maturation (testis descent) was significantly delayed in some groups. For dams and pups alike, simultaneous exposure to both pesticides was not found to have a greater toxic effect than that resulting from exposure to only one of the two. Taken together, these results demonstrate exposure-related influences on several developmental measures. Detection of more subtle effects may be improved through the use of the developmental temporal response protocols utilized in this study.

Developmental toxicity evaluation of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in Wistar rats.

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is a genotoxic chlorination by-product in drinking water. There is some evidence that it has developmental toxic effects in vitro but its potential to cause developmental effects in vivo is not known. The developmental effects were evaluated in Wistar rats. Rats (22-26 dams per dose group) were administered MX by gavage at the dose levels of 3, 30, or 60 mg/kg in water on gestation days 6-19. Control animals received plain water. Clinical signs, body weight, and food and water consumption were recorded for the dams. On gestation day 20, a cesarean section was performed and the ovaries anduterine contents of the dams were examined and the liver, kidneys, spleen, and thyroid glands weighed. The fetuses of all dose groups were weighed, sexed, and observed for external and skeletal malformations and the fetuses of the two highest dose groups were evaluated for visceral malformations. The highest dose, 60 mg/kg of MX, was slightly toxic to the dams. It decreased the corrected body weight gain of dams by 32% and the water consumption by 16-17%. Kidney and liver weights were slightly increased. MX did not affect the number of implantations nor did it cause any resorptions. The body weights of fetuses were not significantly affected. MX did not cause external malformations or skeletal anomalies. Two fetuses at 60 mg/kg and one fetus at 30 mg/kg had major visceral malformations (persistent truncus arteriosus, diaphragmatic hernia, dilated aorta with a stenosis of pulmonary arteries) and two minor artery abnormalities were observed in those animals. The frequency of unilateral displaced testis was slightly higher (9.2%) in the 60-mg/kg dose group than in controls (1.6%). Since the abnormalities did not form a consistent pattern and occurred most at maternally toxic dose, we conclude that MX can be regarded as non-teratogenic.

Effects of prenatal exposure to cocaine on the developing brain: anatomical, chemical, physiological and behavioral consequences.

Earlier studies of human infants and studies employing animal models had indicated that prenatal exposure to cocaine produced developmental changes in the behavior of the offspring. The present paper reports on the results obtained in a rabbit model of in utero exposure to cocaine using intravenous injections (4 mg/kg, twice daily) that mimic the pharmacokinetics of crack cocaine in humans. At this dose, cocaine had no effect on the body weight gain of dams, time to delivery, litter size and body weight or other physical characteristics of the offspring. In spite of an otherwise normal appearance, cocaine-exposed neonates displayed a permanent impairment in signal transduction via the D1 dopamine receptor in caudate nucleus, frontal cortex and cingulate cortex due to an uncoupling of the receptor from its associated Gs protein. This uncoupling in the caudate nucleus was shown to have behavioral consequences in that young or adult rabbits, exposed to cocaine in utero, failed to demonstrate amphetamine-elicited motor responses normally seen after activation of D1 receptors in the caudate. The cocaine progeny also demonstrated permanent morphological abnormalities in the anterior cingulate cortex due to uncoupling of the D1 receptor and the consequent inability of dopamine to regulate neurite outgrowth during neuronal development. Consistent with the known functions of the anterior cingulate cortex, adult cocaine progeny demonstrated deficits in attentional processes. This was reflected by impairment in discrimination learning during classical conditioning that was due to an inability to ignore salient stimuli even when these were not relevant to the task. The impairment in discrimination learning also occurred in an instrumental avoidance task and could be shown to be due to an impairment of cingulothalamic learning-related neuronal coding. It was proposed that the selective loss of D1-related neurotransmission in the anterior cingulate cortex prevented an appropriate activation of GABA neurons and thus a loss of inhibitory regulation that is necessary for processes involved in associative attention. Taken together, these findings suggest that the uncoupling of the D1 receptor from its G protein may be the fundamental source of the anatomic, cognitive and motor disturbances seen in rabbits exposed to cocaine in utero. Moreover, the long-term cognitive and motor deficits observed in the rabbit model are in agreement with the recent reports indicating that persistent attentional and other behavioral deficits may be evident in cocaine-exposed children as they grow older and are challenged to master more complex cognitive tasks.

Prenatal Cocaine Exposure: Long-Term Deficits in Learning and Motor Performancea.

We have developed a rabbit model of in utero exposure to intravenous injections of cocaine given twice daily to dams from gestational days 8-29. At the doses employed (4 mg/kg, injected twice daily), no differences were found in the body weight gain of dams, time to delivery, litter size, and body weight or other physical characteristics of the offspring. However, cocaine-exposed pups displayed an abnormal structural and neurochemical development of the anterior cingulate cortex which persisted into adulthood. In agreement with the known functions of the anterior cingulate cortex, we found that adult, sexually mature rabbits, exposed to cocaine prenatally, demonstrate impairments in motor function, alterations in associative learning and severe impairments in discrimination learning. Moreover, the alterations in discrimination learning were interpreted to be due to deficits in attentional processes. Specifically, cocaine progeny preferentially attend to more salient stimuli even when these are not relevant to the task. Consequently they have difficulty in attending to less salient but relevant stimuli when more salient but irrelevant stimuli occur in the same context. We concluded that the learning deficits are a reflection of the morphologic and neurochemical abnormalities of the anterior cingulate cortex. Alterations in dopamine function of the caudate nucleus may also contribute to the deficits in motor performance.

Zinc protection against cadmium-induced infertility in female rats. Effect of zinc and cadmium on the progesterone production of cultured granulosa cells.

Adult female rats were treated subcutaneously (s.c.) with zinc chloride (ZnCl2, 10 or 20 mg kg-1 body weight, bw) four times during two ovarian cycles. The third injection was accompanied by cadmium chloride (CdCl2) administration sc (2.5, 5 and 10 mg kg-1 bw). The fourth zinc (Zn) treatment was followed by mating. ZnCl2 (20 mg kg-1) itself impaired fertility by 20%, while CdCl2 dose-dependently blocked the receptivity of female rats. In combination with 2.5 and 5 mg kg-1 CdCl2 the metal salts decreased fertility in an additive fashion, whereas at the highest CdCl2 dose (10 mg kg-1) a marked ameliorating effect of ZnCl2 (10 and 20 mg kg-1) on cadmium (Cd)-caused sterility was observed. In the pregnant animals apart from the higher Cd-induced blood progesterone levels and reduced body weight gain of dams, no significant treatment-related maternal and fetal effects could be observed. ZnCl2 (10 to 80 microM) and CdCl2 (10 to 80 microM) were added to the culture medium of ovarian granulosa cells. CdCl2 suppressed follicle-stimulating-hormone- (FSH-) and cAMP-stimulated progesterone accumulation. No protective effect of Zn against Cd-induced drop in progesterone production could be seen, while Zn by itself induced a significant increase in FSH-supported progesterone synthesis. In conclusion, while Zn protected against Cd-induced sterility in vivo, it failed to counteract the direct effect of Cd on steroid biosynthesis. The data indicate that Zn protection does not take place at the level of ovary. Moreover, Zn and Cd seem to affect FSH-stimulated progesterone production by different mechanisms.

Reproductive and developmental toxicity studies of taltirelin hydrate (3) teratogenicity study in rabbits by oral administration

Teratogenicity study of taltirelin hydrate, a thyrotropin releasing hormone analogue, was carried out in Japanese white rabbits. Female rabbits were orally given taltirelin hydrate at a dose of 0 (control), 0.15, 1.5, or 15 mg/kg from day 6 to day 18 of gestation. Females were sacrificed on day 29 and their fetuses were examined. Neither death nor adverse effects on food consumption in dams were found in any dose groups. In the 15 mg/kg group, rapid breathing and decreased body weight gain in dams were temporally observed. No adverse effect of taltirelin hydrate on reproductive function was detected in any groups. In the fetal examination, taltirelin hydrate had no teratogenic, lethal, or growth retardation effects in any groups. These results show that the no-toxic dose levels of taltirelin hydrate are 1.5 mg/kg for general toxicity in dams, and 15 mg/kg for reproductive function of dams and for development of their offspring.

Reproductive effects of prenatal exposure to 5-bromo-2′-deoxyuridine on male rats

5-Bromo-2′-deoxyuridine (BrdU) was administered intraperitoneally to Sprague-Dawley rats at doses of 12.5, 25, 50, or 100 mg/kg/d on days 9 through 15 of gestation, and at 50 or 100 mg/kg/d on days 16 through 20 of gestation. Dams were allowed to deliver naturally and the numbers of live and dead pups were recorded. Male offspring were allowed to mature and then cohabited with untreated female rats for assessment of reproductive performance. Dam body weight gain during pregnancy and lactation periods was not reduced by the treatment with BrdU. Dams treated with 50 and 100 mg BrdU/kg on days 9 through 15 of gestation had litters with decreased survival rates. The male offspring from dams treated with 25, 50, and 100 mg BrdU/kg on days 9 through 15 of gestation had reduced body weights over the course of the entire study. A dose-related decrease in copulation and fertility rates was found in the male offspring of dams treated on days 9 through 15 of gestation, while no significant decrease in those rates were found in the male offspring of dams treated on days 16 through 20 of gestation. Neither histopathologic examination of testes nor sperm examination indicated the cause of the impaired fertility in the male offspring from dams treated with BrdU on days 9 through 15 of gestation. All of the male offspring of dams treated with 100 mg BrdU/kg on days 9 through 15 of gestation failed to copulate, and some of the male offspring of dams treated with 50 mg BrdU/kg on days 9 through 15 of gestation did not form copulatory plugs or formed very small plugs. Dilatation of the lateral ventricles and cysts in the pars distalis of the pituitary were observed in all of the male offspring of dams treated with 100 mg BrdU/kg on days 9 through 15 of gestation. The impaired fertility of the male offspring of dams treated prenatally with BrdU may have resulted from BrdU exposure effects on central nervous system action such as loss of libido and from failure to form proper copulatory plugs, rather than the direct effects of BrdU on the male reproductive organs.

Relationship between moderate food restriction during pregnancy and Fe, Zn and Cu contents in maternal tissues and foetuses.

This study was undertaken to monitor Fe, Zn and Cu contents in several maternal tissues and the products of conception of rats submitted to moderate food restriction during pregnancy. Two groups of female rats, nonpregnant (NP) and pregnant (P1), were fed ad libitum. A second group of pregnant rats (restricted diet, P2) was fed for 14 days with the same intake as NP, then the intake was increased by 5% from day 14 to day 21. A significant decrease in liver Fe content was noted in P1 and P2 pregnant rats on day 21, being more marked in livers of P2. Increases in Cu and Zn contents in liver were induced during pregnancy, but the values were significantly lower in P2 than in P1. On day 21, no significant differences due to food restriction were noted in serum concentrations of these trace elements, placental weight and placental Fe. However, dam body weight gain, placental Zn and Cu contents were reduced in P2. Foetuses of undernourished dams exhibited at term lower weight and smaller amounts of Fe, Zn and Cu than those in P1. These results confirm that moderate food restriction during pregnancy produces intrauterine growth retardation and that newborns have low trace element contents (particularly in Cu), which make them dependent on correct postnatal supply.

Effects of N‐acetyl‐L‐cysteine on Teratogenicity of Cadmium in Mice

ABSTRACT Embryotoxicity and teratogenicity of cadmium (Cd) and modulation of its effects by N‐acetyl‐L‐cysteine (NAC) were evaluated in mice. Pregnant ICR mice were intraperitoneally injected with 3.5 mg/kg of CdCl2 on day 10 or 11 of gestation (vaginal plug = day 0). Pregnant mice were pretreated with 160 mg/kg of NAC intravenously 2 hours before dosing with CdCl2. Pregnant mice were killed on day 17 of gestation. Fetuses were examined for external malformations, especially limb malformations, cleft palate and abnormal palatal rugae. There was little difference in body weight gain of dams during the gestation period in the groups treated with NAC plus Cd as compared with the groups treated with Cd alone. Pretreatment with 160 mg/kg of NAC decreased the fetal mortality, incidence of cleft palate and abnormal palatal rugae induced by Cd on day 11. On day 10, pretreatment with NAC decreased the incidence of Cd induced abnormal palatal rugae. These results clearly indicate that NAC exerts protective effects against embryotoxicity and teratogenicity of Cd.

Reproductive and developmental toxicity studies of 6-amidino-2-naphthyl 4(-)[(4,5-dihydro-1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187). (IV)--Oral administration to New Zealand white rabbits during the period of fetal organogenesis.

Oral administration of 6-amidino-2-naphthyl 4(-)[(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethanesulfonate (FUT-187) at doses of 10, 30 and 100 mg/kg was given to New Zealand White rabbits on days 6 to 18 of gestation. The following results were obtained. Decreased food consumption and suppression of body weight gain in dams were observed and these changes contributed to the increase in aborted or prematured births and increased fetal mortality at the 100 mg/kg group. There were changes attributable to FUT-187 on external, skeletal and visceral examinations of fetuses. Based on the above, the no-effect dose level in dams and fetuses in the present study is 30 mg/kg/day.

Reproductive and developmental effects on rats after prenatal, postnatal, or pre- and postnatal exposure to the hypotensive agent losulazine.

Losulazine was administered orally to 21 bred Sprague-Dawley rats per group at 0, 4, and 8 mg/kg/day by three dosing schedules: gestation day 15 until term (prenatal section); postnatal days 1 to 21 (postnatal section); and gestation day 15 until postnatal day 21 (pre- and postnatal section). Dams were allowed to deliver and the number of live and dead pups recorded. Each pup was sexed and weighed on days 0, 4, and 21. Also, pinna detachment and eye opening were monitored. Randomly selected offspring were allowed to mature and then cohabited for assessment of reproductive performance. Dam body weight gain during dosing was reduced in the high dose group of the pre- and postnatal section. Treated dams in the postnatal and pre- and postnatal sections had litters with reduced body weight, delayed development, and decreased survival. In the F1 mating portion of the postnatal and pre- and postnatal sections, F1 offspring from losulazine-treated dams had reduced body weights over the entire study. A dose-related decrease was found for both the percentage of F1 males that bred and the conception rate of bred F1 females. All F1 females entered estrus at least once, and those that conceived delivered normal litters. Neither microscopic examination of F1 male reproductive organs nor analyses of serum prolactin, luteinizing hormone (LH), and testosterone levels indicated the cause of impaired fertility. Thus, although prenatal exposure only did not result in adverse effects, postnatal exposure to losulazine via lactation affected offspring growth, development, and reproductive capacity.

ラット胎性期に暴露した自律神経作用薬の子の行動発達に及ぼす影響

The drugs used were methamphetamine, reserpine, norepinephrine, epinephrine, propranolol, chlorpromazine, haloperidol, pilocarpine and atropine. Each drug except for reserpine (days 7-13 and 14-19 of gestation) was administered subcutaneously to dams from day 7 to 19 of gestation. The body weight gain of dams receiving reserpine (days 7-13) and haloperidol was inhibited during the gestation period. Two out of 9 dams receiving methamphetamine died on day 21 of gestation period; However, no effect was observed in dams given other drugs. The body weight gain of pups was inhibited in methamphetamine and haloperidol treated groups. The mortality of pups was comparable in all groups. The behavioral development of the righting reflex, cliff drop avoidance and negative geotaxis of pups given reserpine (days 7-13), norepinephrine, chlorpromazine and haloperidol was significantly retarded in comparison with that of control pups. The spontaneous motor activity of pups measured by Animex was increased in reserpine (days 7-13) and epinephrine treated groups and decreased in the chlorpromazine treated group on day 28 postpartum, but comparable in all groups on day 56 postpartum. The conditioned avoidance responses using the shuttle box revealed deficits of avoidance learning of pups in the reserpine (days 7-13), norepinephrine and atropine treated groups. These findings suggest that the prenatal exposure to drugs acting on the autonomic nervous system may produce adverse effects on the behavioral development of pups; However, the adverse effects were more apparent by postnatal exposure than by prenatal exposure.