• Toxicological Research
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• v.19 no.1
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• pp.21-27
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• 2003

A teratogenic study of dimethyl dimethoxy biphenylate derivative (DDB-S) was carried out on Sprague-Dawley rats. DDB-S dissolved in saline was administered to male and female rats by intravenously injection at daily doses of 50 mg/kg, 75 mg/kg, and 100 mg/kg. A half of dams were sacrificed at 20th day of gestation to scrutinize the pregnant performances and fetal development. And the remaining dams were allowed to deliver. The growth, reflex, behaviour and reproductive function of F1 offsprings were examined. There was no treatment-related difference in body weight, food consumption and necropsy findings of dams. No gross, skeletal and visceral abnormalities was observed in F1 fetuses from dams treated with DDB-S. F1 offsprings did not show any treatment-related difference in growth, reflex, behaviour and reproductive performance. At caesarean section of F1 dams, no growth retardation and gross abnormality was observed in F2 fetuses. In conclusion, DDB-S did not show any potential teratogenic effect in rats.

• Development and Reproduction
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• v.5 no.2
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• pp.175-180
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• 2001

The ectopic expression of gonadotropin releasing hormone(GnRH and luteinizing hormone(LH) in several tissues is a quite intriguing phenomenon. Recently, the presence of GnRH and its receptor has been clearly demonstrated in rodents and human mammary gland. In this context, one can postulate that the presence of local circuit composed of GnRH and LH in the gland. The present study was undertaken to elucidate whether there is a correlation between the LH expression in rat mammary gland and physiological status during the process of mammary differentiation. LH contents in mammary gland from cycling to weaning rats were measured by radioimmunoassay(RIA). In cycling rats, changes of the LH level in both serum and mammary gland showed similar pattern as the highest level in proestrus and the lowest level in diestrus II stage. While the serum LH levels were fluctuated from pregnant through involution stage, a sharp decline of mammary LH contents was observed in the lactating rats. This decrement was recovered in involuting rats to the level of proestrus stage. Reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analyses demonstrated that the transcriptional activities of the mammary LH and GnRH were increased from diestrus I stage to estrus stage, and the increased levels were maintained in pregnant, lactation and involution stages. To test the hypothesis that the alteration in mammary LH expression might be steroid-dependant, ovariectomy(OVX) and steroid supplement model was employed. As expected, supplement of estradiol(E$_2$) after OVX remarkably decreased serum LH level compared to that in serum from vehicle-only treated rats. Likewise, administration of E$_2$ significantly reduced the mammary LH content. The present study demonstrated that (i) the LH expression in mammary gland could be altered by some physiological parameters such as estrous cycle, pregnancy, lactation and involution, and (ii) ovarian steroid especially estrogen seems to be one of major endocrine factors which are responsible for regulation of mammary LH expression.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.4
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• pp.429-437
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• 2017

The aim of this study was to evaluate the relaxant and anti-inflammatory effects of two thalidomide analogs as phosphodiesterase-4 (PDE-4) inhibitors in pregnant rat uterus. Uteri from Wistar female rats were isolated at 19 day of pregnancy. Uterine samples were used in functional studies to evaluate the inhibitory effects of the thalidomide analogs, methyl 3-(4-nitrophthalimido)-3-(3,4- dimethoxyphenyl)-propanoate (4NO2PDPMe) and methyl 3-(4-aminophthalimido)- 3-(3,4-dimethoxyphenyl)-propanoate (4APDPMe), on prostaglandin-$F2{\alpha}$ ($PGF2{\alpha}$)-induced phasic, $K^+$-induced tonic, and $Ca^{2+}$-induced contractions. Accumulation of cAMP was quantified in uterine homogenates by ELISA. Anti-inflammatory effect was assessed by using ELISA for determination of the pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ ($TNF{\alpha}$) and interleukin (IL)-$1{\beta}$, and anti-inflammatory IL-10, from uterine explants stimulated with lipopolysaccharide (LPS). Nifedipine, forskolin and rolipram were used as positive controls where required. Both thalidomide analogs induced a significant inhibition of the uterine contractions induced by the pharmaco- and electro-mechanic stimuli. Nifedipine and forskolin were more potent than the analogs to inhibit the uterine contractility, but these were more potent than rolipram, and 4APDPMe was equieffective to nifedipine. Thalidomide analogs increased uterine cAMP-levels in a concentration-dependent manner. The LPS-induced $TNF{\alpha}$ and $IL-1{\beta}$ uterine secretion was diminished in a concentration-dependent fashion by both analogs, whereas IL-10 secretion was increased significantly. The thalidomide analogs induced utero-relaxant and anti-inflammatory effects, which were associated with the increased cAMP levels as PDE-4 inhibitors in the pregnant rat uterus. Such properties place these thalidomide analogs as potentially safe and effective tocolytic agents in a field that urgently needs improved pharmacological treatments, as in cases of preterm labor.

• Korean Journal of Animal Reproduction
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• v.16 no.1
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• pp.21-38
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• 1992

The present study was carried out to investigate morphologic changes in the corpus luteum of the pregnant rat by electron microscope after administration of prostaglandin F2$\alpha$(PGF2$\alpha$). Pregnant rates were treated with PGF2$\alpha$(1,500$\mu\textrm{g}$/rat) and their corpura lutea were observed morphologically. The results obtained in this study were summarized as follows ; 1. The weight of the ovaries and corpura lutea were decreased slightly at 8~24 hours after PGF2$\alpha$ administratin but no significant differences were observed. 2. The number of corpora lutea and luteal cells decreased slightly at 12~48 hours and 18~24 hours after PGF2$\alpha$ tretment but there were no signifciant differences between control and treatment. 3. The weight of uterus and the unmber of embryo decreased slightly at 96 hours and at 18~96 hours after PGF2$\alpha$ administration but no significant differences were obtained. 4. In the electron microscopic observatons, lipid droplets which are electron dense and appear in the cytoplasm moderately increased in number after PGF2$\alpha$ treatment. The lipid droplets were surrounded by mitochodria and appeared in the autophagic vacuoles. 5. Moderated and high electron dense mitochondria which are round or elongated in shape showed pleomorphism from 3 hours after PGF2$\alpha$ treatment. Destruction of tubular of vesicular cristae was observed at 6 hours after the treatment. Dense body and myelin figures in matrix of mitochondria were also appeared. 6. Well-developed smooth endoplasmic reticulum(sER) showed tubular or vesicular cisternae. A number of whorl membranes containing ribosomes, mitochondria and lipid droplets were observed at 1.5 hour after treatment. sER was abundant in luteal cells at 12 hours were treatment. 7. Well-developed Golgi pparatus appeared obviously 6 hours and more prominently at 12 hours. Those Golgi vesicles were remarkably dilated. 8. Generally, a few rough endoplasmic reticulum (rER) were appeared after treatment and cisternae showed slight dilatation. No differences among the treatments were observed. However, slight dilation of cisternae was observed at 1.5 hours after treatment. 9. Ribosomes composed of free and polyribosomes were abundant before treatment but polyribosomes were appeared at 12 to 24 hours after treatment. 10. Intercellular space were slightly extended at 3 hours and markedly extended at 12 hours. Numerous microvillous protrusions were observed at these times. Membranous multivesicular structures and autophagic vacuoles were also appeared in the intercellular space. 11. At 3 hours after the treatment, autophagic vacuoles appeared in the cytoplasm of the cell. They increased in number with time and were observed to transfer to the intercellular space. Lysosomal dense body appeared in the cytoplasm and the inclusion body was also observed in nucleus at 12 to 24 hours after treatment.

• Journal of Oriental Neuropsychiatry
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• v.9 no.2
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• pp.45-51
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• 1998

Purpose : This study has an experiment on finding how Hyangbujapamultang advanced the learning and memory of rat to find the method to improve the failure of memory which is the symptom of dementia.Method : In the experiment, rats were divided the control group (14 rat) which medicate the excipient into the sample group (17 rat) which medicates Hyangbujapalmutang. And the learning ability test and the memorv test was practiced to using the task of radial arm maze.The learning ability test had the presupposition that, when a rat which frequents 8 tracks makes am error not exceeding one time for 3 days without a break, it passes the test.First experiment compared total days when the control group passed the test with total days when the sample group it.The memory test practiced after 24 hours when the learning ability test was over. When a rat frequents 4 tracks, the gates is cut off during 30 seconds. Here the number of error at the control group with that of the sample group.Result: In the learning ability test, the sample group needed 5.82${\pm}$0.37 days to pass the test and the control group needed 6.43${\pm}$0.67 days. In the memory test, the sample group errored 0.29${\pm}$0.37 times and the control group errored 1.86${\pm}$0.78 times.Conclusion : In the learning ability test, the sample group passed the test earlier than the control group, but any statistical correlationship couldn't be found in it. In the memory test, the sample group had the pregnant reduction of the number of error in comparison with the control group.

• Journal of Nutrition and Health
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• v.16 no.4
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• pp.287-295
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• 1983

Sprague Dawley pregnant rats were fed the hydrogenated coconut oil (P/S 0.02), corn-oil plus beef tallow (P/S 1.0), and corn-oil(P/S 4.0)diet during the 14 days of gestation and through lactation. At weaning, offsprings from each group were divided into two and corn- oil diet was switched to coconut and vice versa, while the other corresponding groups continud the same diet. Body, brain, and liver weights were measured on pups and the brains were analyzed for DNA and vitamin E. Serum and liver vitamin E levels were alse measured. Body weight of coconut group was significantly low throughout the 7 week period, but brain weight was significantly depressed before weaning. Liver weight showed similar pattern with the body weight. Serum vitamin levels increased before weaning, while tissue vitamin E increased after weaning. Serum vitamin E levels of switched groups were similar to that of P/S 1.0 group. Brain vitamin E levels per DNA of switched groups were also similar to that of P/S 1.0 group. And the effect of different dietary essential fatty acid levels on vitamin E in the brain during lactation found to be insignificant.

• Journal of radiological science and technology
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• v.41 no.2
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• pp.157-162
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• 2018

This study is a search for radiation protection effects of radiation exposure on the organogenic period during the prenatal period, which is known to be the most likely to have congenital malformations by radiation exposure. To study the radiation protection for the mixture of selenium that is strong antioxidant and folic acid that is essential vitamin for DNA synthesis, 2 Gy of radiation was irradiated to pregnant female rats. then, after 14 days of fetal birth, observing blood components, SOD(Superoxide Dismutase), histological changes and external malformations. There was a significant protective effect to reduce blood cell damage(p<0.05) in the irradiation group after selenium and folic acid mixture were administered than irradiation group, and the activation of SOD which is antioxidant enzymes was increased. In addition, confirmed the effect of suppressing the expression of apoptosis of small intestinal cells and the reduction of cerebral cortex layer reduction by radiation. thus, it was confirmed that the congenital malformations were reduced as a result of these protective effects. Based on these results, selenium and folic acid mixture may reduce the incidence of congenital malformations, and it will reduce the damage of the fetus caused by the exposure of the organogenic period due to accidents.

• Imaging Science in Dentistry
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• v.30 no.3
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• pp.159-168
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• 2000

Purpose: To elucidate the effects of the irradiation and calcium-deficient diet on expression of interleukin (IL)-1 during tooth formation of rat molar. Materials and Methods: The pregnant three-week-old Spague-Dawley rats were used for the study. The control group was non-irradiation/normal diet group, and the experimental groups were irradiation/normal diet group and irradiation/calcium-deficient diet group. The abdomen of the rats on the 9th day of pregnancy were irradiated with single dose of 350 cGy, The rat pups were sacrificed on the 14th day after delivery and the maxillae tooth germs were taken. The specimen were prepared to make sections for light microscopy, and some of tissue sections were stained immunohistochemically with anti-IL-l antibody. Results: In the irradiation/normal diet group, dental follicle showed fewer blood vessels, mononuclear cells, and fusions of mononuclear cells than in non-irradiation/normal diet group. Alveolar bone showed a few osteoblasts and osteoclasts. Periodontal ligament showed collagen fibers and fibroblasts with irregularity. Weak immunoreactivity for IL-l was shown in dental follicle, alveolar bone, and periodontal ligament. In the irradiation/calcium-deficient diet group, dental follicle showed sparse cellularity. Alveolar bone showed diminished number of osteoblasts. Periodontal ligament showed irregular collagen fibers and atrophy of cementoblasts and fibroblasts. No immunoreactivity for IL-1 was shown in dental follicle, alveolar bone, and periodontal ligament. Conclusion: Irradiation and calcium-deficient diet seems to cause disturbance of the expression of interleukin-l during tooth formation of rat molar.

• Imaging Science in Dentistry
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• v.30 no.3
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• pp.169-181
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• 2000

Purpose: To investigate the expression of bone morphogenetic protein (BMP)-2/4 during eary tooth development after irradiation and calcium-deficient diet. Materials and Methods: The pregnant three-week-old Sprague-Dawley rats were used for the study. The control group was non-irradiation/normal diet group (Group 1), and the experimental groups were irradiation/normal diet group (Group 2) and irradiation/calcium-deficient diet group (Group 3). The abdomen of the rats at the 9th day of pregnancy were irradiated with single dose of 350 cGy. The rat pups were sacrificed at embryonic 18 days, 3 days and 14 days after delivery and the maxillae tooth germs were taken. The tissue sections of specimen were stained immunohisto-chemically with anti-BMP-2/4 antibody. Results: At embryo-18 days, immunoreacivity for BMP-2/4 of the Group 1 was modetate in stratum intermedium of dental organ and weak in dental papilla and dental follicle, but that of Group 2 was weak in cell layer of dental organ, and no immunoreacivity was shown in dental papilla and dental follice of Group 2 and in all tissue components of the Group 3. At postnatal-3 days, immunoreacivity for BMP-2/4 of the Group 1 was strong in cell layer of dental organ, odontoblasts and developing alveolar bone, but that of Group of 2 and Group 3 was weak in odontoblasts and developing alveolar bone. At postnatal-14 days, immunoreacivity for BMP-2/4 of the Group 1 was strong in newly formed cementum, alveolar bone and odontoblasts, but that of Group 2 was weaker than that of Group 1. In the Group 3, tooth forming cell layer showed weak immunoreactivity, but other cell layers showed no immunoreactivity. Couclusion : The expression of bone morphogenetic protein (BMP)-2/4 during early tooth development was disturbed after irradiation and calcium-deficient diet.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2002.11a
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• pp.34-36
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• 2002

Epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) have been shown to stimulate proliferation and differentiation of various somatic cells, including placental trophoblasts and also to enhance fetal growth and development when maternally administered. Since an increase of the expression of placental EGF and IGF-I receptors in rat, mouse, and human with the gestation advanced, both EGF and IGF-I were considered to play pivotal roles on fetal growth by regulating some function of placental cells. Amino acids are crucial importance for both maternal and fetal requirements of energy source and essential constituent of fetal mass during pregnancy. Impaired fetal and placental uptake of amino acids has been observed in several models of growth retardation in the rat. Amino acid is concentrated in the fetal side through active transport by amino acid transporters and is one of the important metabolic fuels for the fatal growth. Therefore, at first plasma amino acid concentrations in mothers and fetuses were measured as an index of uphill transport across the placenta associated with EGF and IGF-1. The EGF administration at the concentration of 0, 0.1, or 0.2 $\mu\textrm{g}$/g to pregnant rats from day 18 to 21 of gestation apparently increased fetal/maternal ratio of serum proline concentration and also fatal growth in EGF dose-dependent manner. When IGF-I in doses of 0, 1, 2, and 4 $\mu\textrm{g}$/g were administrated, the ratio of leucine, isoleucine, tryptophan, phenylalanine, tyrosine and also fetal growth significantly increased with a dose-dependent manner. These results suggested that EGF and IGF-I enhanced fatal growth by, as one of its possible mechanisms, promoting placental activity to transfer some amino acid supplies from the mother to the fetus in late pregnancy.