• Toxicological Research
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• 제11권1호
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• pp.81-89
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• 1995

A teratogenicity study of KTC-1, a new semisynthetic rifamycin antituberculous drug, was conducted in Sprague-Dawley rats. Dosages of KTC-1 0, 7, 21, and 63 mg/kg/day were administered to darns orally gayage from day 7 to day 17 of gestation. Two-third of dams per group were subjected to cesarean section on day 21 of pregnancy for examination of their fetuses, and the remaining one-third of darns per group were allowed to deliver naturally for postnatal examination of their offspring. At 21 mg/kg/day, an increase in the skeletal variations of F1 fetuses and a decrease in the body weight of F1 offspring were seen. At 63 mg/kg/day, a loss in body weight was observed in darns. An increase in fetal death rate, a decrease in litter size and body weight, and an increase in the incidence of visceral malforrnations and skeletal variations were found in F1 fetuses. In particular, lumar rib occurred at an incidence of 31%. In addition, an increase in the dead newborns at birth and neonatal deaths during the lactation period, a loss in body weight, and a decrease in spleen weight were observed in F1 offspring. There were no signs of maternal toxicity or embryotoxicity at 7 mg/kg/day. The results suggest that the no-effect dose level(NOEL)for dams is 21 mg/kg/day, and NOELs for F1 fetuses and offspring are 7 mg/kg/day.

• Toxicological Research
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• 제11권1호
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• pp.91-101
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• 1995

A perinatal and postnatal study of KTC-1, a new semisyntheitic rifamycin antituberculous drug, was conducted in Sprague-Dawley rats. Dosages of KTC-1 0, 12, 27.6, and 63.5 mg/kg/day were administered to dams orally by gavage from day 17 of gestation to day 21 of lactation. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. At 63.5 mg/kg/day, weakness, dark-red discharge around eyes, a loss in body weight, and a decrease in food and water consumption were observed in dams. An increase in the weight of adrenal gland and spleen, and a decrease in the weight of kidney and heart were also found. An increase in neonatal deaths during the lactation period, a loss in body weight, a delay in physical development, a decrease in traction ability, an increase in the number of errors and the time required for the multiple T-maze trial were found in F1 offspring. In addition, an increase in the incidence of visceral variations and retarded ossification were observed in F1 4 day old rats. An increase in the incience of skeletal anomalies was seen in F2 fetuses. There were no sings of maternal toxicity or embryotoxicity at 12 and 27.6 mg/kg/day. From the results mentioned above, it can be concluded that the no-effect dose levels(NOELs)for dams, F1 offspring, and F2 fetuses are 27.6 mg/kg/day.

• Journal of Animal Science and Technology
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• 제59권1호
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• pp.1.1-1.11
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• 2017

Background: Intrauterine environment plays a pivotal role in the origin of fatal diseases such as the metabolic syndrome. Diabetes is associated with low-grade inflammatory state and dysregulated adipokines production. The aim of this study is to investigate the effect of maternal diabetes on adipocytokines (adiponectin, leptin and TNF-${\alpha}$) production in F1 offspring in rats. Methods: The offspring groups were as follows: F1 offspring of control mothers under control diet (CD) (CF1-CD), F1 offspring of control mothers under high caloric diet (HCD) (CF1-HCD), F1 offspring of diabetic mothers under CD (DF1-CD), and F1 offspring of diabetic mothers under HCD (DF1-HCD). Every 5 weeks post-natal, 10 pups of each subgroup were culled to obtain blood samples for biochemical analysis. Results: The results indicate that DF1-CD and DF1-HCD groups exhibited hyperinsulinemia, dyslipidemia, insulin resistance and impaired glucose homeostasis compared to CF1-CD (p > 0.05). DF1-CD and DF1-HCD groups had high hepatic and muscular depositions of TGs. The significant elevated NEFA level only appeared in offspring of diabetic mothers that was fed HCD. DF1-CD and DF1-HCD groups demonstrated low serum levels of adiponectin, high levels of leptin, and elevated levels of TNF-${\alpha}$ compared to CF1-CD (p > 0.05). These results reveal the disturbed metabolic lipid profile of offspring of diabetic mothers and could guide further characterization of the mechanisms involved. Conclusion: Dysregulated adipocytokines production could be a possible mechanism for the transgenerational transmittance of diabetes, especially following a postnatal diabetogenic environment. Moreover, the exacerbating effects of postnatal HCD on NEFA in rats might be prone to adipcytokine dysregulation. Furthermore, dysregulation of serum adipokines is a prevalent consequence of maternal diabetes and could guide further investigations to predict the development of metabolic disturbances.

• Journal of Acupuncture Research
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• 제23권3호
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• pp.47-56
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• 2006

Methods : 40 of Female rats were allowed to mate with 40 of male rats. Then, female rats were delivered of offspring rats, After birth 28 days, offspring rats were divided 8 groups, The normal group(Group A), the 10 mg/kg Angelicae gig antis radix~treated group(Group B), the 50 mg/kg Angelicae gigantis radix-treated group(Group C), the 100 mg/kg Angelicae gig antis radix-treated group(Group D), The control (noise-treated) group(Group E). the noise -10 mg/kg Angelicae gigantis radix-treated group(Group F), the noise-50 mg/kg Angelicae gigantis radix~treated group(Group G), and the noise-100 mg/kg Angelicae gigantis radix-treated group(Group H)(n = 5 in each group), From the 15th day of pregnancy, all rats were subcutaneously injected with 50 mg/kg BrdU once a day 30 min before the starting of experimental treatment. Rats of the prenatal noise-treated group were applied with 95 decibel supersonic machine sound for 1h once a day until delivery, After birth 28 days, offspring rats intraperitoneally injected with 50 mg/kg of BrdU and offspring rats were treated Angelicae gigantis radix Herb-acupunture on chungwan(CV12) for 7 consecutive days. For the detection of BrdU-positive cells and Ki-67 positive cells in hippocampus, immunohistochemistry was performed. Results : 1. The number of BrdU-positive cells in the dentate gyrus of noise-treated group was significantly decreased to normal group, and the Group F, G, H were significantly increased to control group. 2. The number of Ki-67 positive cells in the dentate gyrus of noise-treated group was significantly decreased to control group, and the Group G, H were significantly increased to control group. Conclusion : We concluded that postnatal Angelicae gigantis radix administration has effect on cell proliferation in offspring rats with prenatal noise stress during pregnancy.

• Biomolecules & Therapeutics
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• 제3권1호
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• pp.38-46
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• 1995

DA-125, a new anthracycline antitumor antibiotic, was administered at dose levels of 0, 0.04, 0.2 and 1.0 mg/kg/day intravenously to pregnant and subsequently delivered Sprague-Dawley rats from day 17 of gestation to day 21 of lactation. Effects of test agent on general toxicity of dams and growth, behaviour and mating performance of F1 offspring were examined. At 1 mg/kg, one out of the twentytwo dams showed difficult delivery, characterized by a stillbirth. Reduction in body weight, loss in food intake, and decrease in spleen weight were also observed in dams. In addition, the lower rates of successful performances in memory test (28.6%) and necrosis of tail end (9.5%) were seen in F1 offspring. At 0.04 and 0.2 mg/kg, no toxic effect on dams and F1 offspring was observed. There were no malformed Fl and F2 fetuses in all groups. The results indicate that the no effect dose levels(NOELs) of DA-125 are 0.2 mg/kg/day for dams and Fl offspring, and over 1 mg/kg/day for F2 fetuses.

• Biomolecules & Therapeutics
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• 제4권1호
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• pp.59-67
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• 1996

A new composite antibiotic, SM-101(sulbactam·metampicillin), was at dose levels of 0, 375, 750 and 1500 mg/kg/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. Two-third of dams per group were subjected to caesarean section on day 20 of pregnancy and the remaining 10 dams per group were allowed to deliver. Effects of test substance on dams, embryonal development of F1 fetuses, as well as growth, behaviour and mating performance of F1 offspring were examined. In dams, two deaths occurred at 375 and 1500 mg/kg, respectively. The decrease in the weight of adrenal glands of the 1500 mg/kg group was observed. The prolongation of pregnancy period was found at 1500 mg/kg. F1 fetuses showed no changes related to the treatment of SM-101. In F1 offspring, the increase in spleen weight was seen at all doses treated. No treatment-related abnormalities were observed in each treated group in terms of development, behaviour and reproductive performance. In F2 fetuses, no drug-induced abnormalities occurred at all doses. The results show that the no-effect dose levels (NOELS) for dams and Fl offspring are under 375 mg/kg/day and NOELs for F1/F2 fetuses are over 1500 mg/kg/day.

• Biomolecules & Therapeutics
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• 제4권4호
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• pp.339-348
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• 1996

A new composite antibiotic, SM-101 (sulbactam·metampicillin), was at dose levels of 0, 250, 500 and 1000 mg/kg/day administered intravenously to pregnant and subsequently delivered Sprague-Dawley rats from day 17 of gestation to day 21 of lactation. Effects of test agent on dams and growth, behaviour and mating performance of Fl offspring were examined. In dams, one death occurred at 1000 mg/kg. The increase in kidney weight of the 250, 500 and 1000 mg/kg group was found. In F1 offspring, both delayed incisors eruption and decreased body weight were observed in females of the 1000 mg/kg group. The increase in the weights of liver and kidney was found in males of the 1000 mg/kg group. No treatment-related abnormalities were observed in each treated group in terms of behaviour and reproductive performance. In F1/F2 fetuses, no drug-induced abnormalities occurred at all doses tested. The results show that the no effect dose level (NOEL) of SM-101 is under 250 mg/kg/day for dams and 500 mg/kg/day for F1 offspring, and over 1000 mg/kg/day for F1/F2 fetuses.

• 한국발생생물학회지:발생과생식
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• 제27권4호
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• pp.195-203
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• 2023

Exposure to environmental chemicals, including endocrine-disrupting chemicals, during the gestational period can have profound adverse effects on several organs in offspring. Bisphenol A (BPA) can infiltrate the human body through food and drinks, and its metabolites can cross both the placental and the blood-brain barriers. In this study, we investigate the effect of gestational exposure to BPA on epigenetic, biochemical, and histological modifications in the uterine tissues of F1 adult offspring rats. Pregnant rats were exposed to BPA from gestational day 8-15, and changes in global DNA methylation in uterine tissues obtained from adult offspring born to the exposed mothers were analyzed. Global DNA methylation analysis revealed that gestational exposure to BPA resulted in DNA hypomethylation in the uterus. Progesterone receptor (PR) protein expression in uterine tissues was monitored using western blot analysis, which revealed that the PR protein content was considerably higher in all BPA-exposed groups than in the control. Immunohistochemical examination for the PR revealed that intense PR-positive cells were more frequently observed in the BPA-exposed group than in the control group. To date, the evidence that the upregulation of PRs observed in the present study was caused by the non-methylation of specific PR promoter regions is lacking. Conclusively, these results indicate that exposure to BPA during gestation induces epigenetic alterations in the uteri of adult female offspring. We speculate that the global DNA hypomethylation and upregulation of the PR observed simultaneously in this study might be associated with the uterus.

• Toxicological Research
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• 제9권1호
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• pp.83-98
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• 1993

LBD-007, a newly developed recombinant human interferon alpha A, was at dose levels of 0, 3 $\times$ $10^6$, 6 $\times$ $10^6$ and 12 $\times$ $10^6$ IU/kg/day administered subctaneously to pregnant Sprague-Dawley rats during the organogenetic period. Ethylenethiourea was used as a positive control. 2/3 of dams per group were subjected to caesarean section on day 20 of pregnancy and the remaining 10 dams per group were allowed to deliver. Effects of test substance on dams, embryonal development development of F1 fetuses, as well as growth, behaviour and mating performance of F1 offspring were examined. 1. No treatment-related changes in clinical signs, food consumption, body weight and necropsy findings of dams were observed.

• Toxicological Research
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• 제9권1호
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• pp.107-118
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• 1993

LBD-007, a newly developed recombinant human interferon alphaA, was at dose levels of 0.3 $\times$$10^6$ , 6 $\times$ $10^6$ and 12 $\times$ $10^6$ IU/kg/day administered subcutaneously to pregnant and subsequent delivered SpragueDawley rats from day 17 of gestation through day 21 of lactation. Effects of test substance on dams and growth, behaviour and mating performance of F1 offspring were examined. 1. No treatmene-related changes in clinical signs, food consumption, body weight, pregnant period and necropsy findings were observed in dams.