• Korean Journal of Veterinary Research
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• v.32 no.4
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• pp.481-487
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• 1992

The present study was designed to investigate the appearance of the congenital aggregates of the ectodermal glial cells in the brain of the normal rodents. The brain samples were taken from mice fetus, juvenile mice, rats and rabbits. The appearance regions of the glial cell aggregates (GCA) were investigated and the cells in the GCA were identified with electron microscope. 1. GCA in the mouse fetus tended to be higher in cell density, larger in size and lower frequency in appearance than juvenile mouse. The regions of higher appearance frequency of GCA in the juveniles of mice, rats and rabbits were ordered as subependymal layer in the collateral trigone of lateral ventricles, molecular layer of the neocortex, inner layer except the molecular layer in the neocortex, cerebral medulla, corpus callosum and hippocampus. Appearance frequency of GCA in the neonatal mice tended to be higher until 5 day after birth, and were markedly decreased on 10 and 15 day after birth. 2. GCA tended to be closed on one side of the blood vessels or neurons but not perivascular or perineuronal appearance. 3. In electron microscophy, GCA were composed of immature oligodendrocytes and astrocytes in the subependymal, and tended to be more mature and loose in the neocortex and to be appended some microglia cells with age. The cells in the GCA of older mice tended to be more mature than in young mice.

• Development and Reproduction
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• v.21 no.4
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• pp.441-448
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• 2017

Bisphenol-A(BPA) is a member of alkylphenol family, and shows adverse effects including reduced fertility, reproductive tract abnormalities, metabolic disorder, cancer induction, neurotoxicity and immunotoxicity. In the present study, we conducted Hershberger assay to evaluate whether the two candidates to replace BPA have androgenic or antiandrogenic activity. The assay was carried out using immature castrated Sprague-Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were BPA, isosorbide (ISO) and cyclohexanedimethanol (CHDM). The rats were necropsied, and then the weights of five androgen-dependent tissues [ventral prostate, seminal vesicle, levator ani-bulbocavernosus (LABC) muscle, paired Cowper's glands, and glans penis] and three androgen-insensitive tissues (kidney, spleen and liver) were measured. All test materials including BPA did not exhibit any androgenic activity in the assay. On the contrary, antiandrogen-like activities were found in all test groups, and the order of the intensity was CHDM > BPA > ISO in the five androgen-sensitive tissues. There was no statistical difference between low dose treatment and high dose treatment of BPA group as well as ISO group. In CHDM group, high dose treatment exhibited most severe weight reduction in all measured tissues. There was no statistical difference in androgen-insensitive tissue measurements, except BPA groups. Since the effects of ISO treatment on the accessory sex organs were much less or not present at all when compared to those of BPA, ISO could be a strong candidate to replace BPA. CHDM treatment brought most severe weight reduction in all of androgen-sensitive tissues, so this material should be excluded for further screening of BPA substitute selection.

• Development and Reproduction
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• v.22 no.1
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• pp.19-27
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• 2018

In the present study, we employed Hershberger assay to determine possible androgenic or antiandrogenic activities of three di-2-ethylhexyl phthalate (DEHP) substitute candidates. The assay was carried out using immature castrated Sprague-Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were DEHP, 2-ethylhexyl oleate (IOO), 2-ethylhexyl stearate (IOS) and triethyl 2-acetylcitrate (ATEC). The rats were necropsied, and then the weights of five androgen-dependent tissues [ventral prostate, seminal vesicle, coagulating glands, levator ani-bulbocavernosus (LABC) muscle, paired Cowper's glands, and glans penis] and four androgen-insensitive tissues (kidney, adrenal glands, spleen and liver) were measured. All test materials including DEHP did not exhibit any androgenic activity in the assay. On the contrary, antiandrogen-like activities were found in all test groups, and the order of the intensity was ATEC < DEHP < ISO < IOO in the five androgen-sensitive tissues. There was no statistical difference between low dose treatment and high dose treatment of all replacement candidate groups. In DEHP groups, high dose treatment exhibited significant weight gains in LABC and Glan Penis. There was no statistical difference in androgen-insensitive tissue measurements. Since the effects of ATEC treatment on the accessory sex organs were much less or not present at all when compared to those of DEHP, ATEC could be a strong candidate to replace DEHP. IOO treatment brought most severe weight reduction in all of androgen-sensitive tissues, so this material should be excluded for further screening of DEHP substitute selection.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2002.10a
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• pp.168-168
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• 2002

To establish a test protocol for the rodent 20-day thyroid/pubertal assay, flutamide and diethylstilbestrol (DES) were administered to intact male Sprague-Dawley rats from postnatal day 33 for 20 days. Flutamide (1, 5, and 25 mg/kg/day) or DES (10, 20, and 40 ug/kg/day) was given once daily by oral gavage to immature male rats. Prepuce separation was significantly delayed in flutamide group and in DES group. One day after the last dose, the rats were killed and pituitary, thyroid, and reproductive organs were removed and weighed. Flutamide treatment resulted in a significant reduction in the weights of epididymides, ventral prostate, seminal vesicles plus coagulating glands and fluid (SVCGF), levator ani. bulbocarvenus muscles (LABC), Cowper's glands, and glans penis. The weight of adrenal glands decreased at % mg/kg/day, while testes and any other organ weights were unaffected. No microscopic changes were observed in the thyroid glands. Serum levels of testosterone wert significantly increased in the flutamide-treated groups and serum levels of estradiol were also increased. A significant reduction in the weights of testes, epididymides, ventral prostate, SVCGF, LABC, Cowpers glands, and glans penis of DES treated group. Serum testosterone and LH decreased significantly in DES group. Decrease of estradiol was observed, but not significant. These results indicate that flutamide and DES delay puberty in the male rat and its mode of action appears to be via altered secretion of steroids, which subsequently affect the development of the reproductive tract. (Supported by the grant from NITR/Korea FDA for Endocrine Disrupter Research.)

• Maxillofacial Plastic and Reconstructive Surgery
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• v.22 no.3
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• pp.274-287
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• 2000

The use of dental implants has increased tremendously in recent years and is expected to increase even more in the future. The successful outcome of any implant procedure is surely dependent on interrelationship of the various components of an equation that includes biocompatibility of implant material, macroscopic and microscopic nature of the implant surface, the status of implant bed, surgical technique, undisturbed healing phase and subsequent prosthetic design and long-term loading phase. The purpose of this study was to clarify the effects of adrenalectomy on the osseointegration of pure titanium implants. Seventy rats, 11 weeks of age, were divided into two groups : an adrenalectomized group and a control group. Titanium screw implant(diameter, 2.0mm; length, 3.5mm) was placed into left tibia of 70 rats, 35 in control group and 35 in the experimental group. The rats were sacrificed at different time interval (1, 2, 3, 4, 6, 8, and 12 weeks after implantation) for histopathologic observation, histomorphometric analysis and immunohistochemistry with fibronectin and CD44 antibody. The results obtained from this study were as follows: 1. Histopathogically, findings, newly formed bone was seen at 3 weeks control group and became lamellar bone at 12 weeks. At 6 weeks, lipocytes were observed in bone marrow space. Thickness of regenerated trabecular bone increased till 6 weeks after then, that decreased gradually. 2. By histomorphometric analysis, marrow bone density and contact ratio of marrow bone to implant decreased significantly from 8 to 12 weeks in experimental group compared to control group and also total bone to implant contact ratio decreased significantly from 4 to 12 weeks in experimental group compared to control group. 3. Fibronectin immunoreactivity was very strong at 3 and 4 weeks control group. And after that reduced gradually. But it was continuously strong from 1 to 12 weeks experimental group. 4. CD44 immunoreactivity was very strong in the newly formed osteoblasts at 3 and 4 weeks control group. But it reacted minimally later. However, it reacted continuously strong from 3 to 12 weeks experimental group. From these results, bone to implant contact ratio decreased gradually from 4 weeks in adrenalectomized group compared to control group. CD44 and fibronectin immunoreactivities were strong at all times in adrenalectomized rats. Therefore, it could be stated that immature bone remained continuously for a long time and not readily proceeded into mature status.

• Journal of Ginseng Research
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• v.48 no.3
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• pp.333-340
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• 2024

Background: Korean red ginseng (KRG) is a product from ginseng roots, which is enriched with ginsenosides and has been utilized for a long time as an adaptogen to alleviate various physiological or disease conditions. While KRG is generally considered safe, conducting a thorough toxicological assessment of the spray-dried powder G1899 during the juvenile period is essential to establish its safety profile. This study aimed to assess the safety of G1899 during the juvenile period using Sprague-Dawley rats. Methods: Two studies were conducted separately: a juvenile toxicity study and a uterotrophic bioassay. To assess the potential toxicity at systemic, postnatal developmental, and reproductive levels, G1899 was orally gavaged once a day in post-weaning juvenile Sprague-Dawley (SD) rats at 0, 1250, 2500, or 5000 mg/kg/day. Estrogenicity was assessed by orally gavaging G1899 in immature female SD rats at 0, 2500, or 5000 mg/kg/day on postnatal days (PND) 19-21, followed by a uterotrophic bioassay. These studies were conducted in accordance with the Good Laboratory Practice (GLP) regulations and regulatory test guidelines. Results: Regarding juvenile toxicity, no abnormalities related to the G1899 treatment were observed in any group during the experiment. Moreover, no uterotrophic responses were observed in the dosed female group. Based on these results, the no observed adverse effect level (NOAEL) of G1899 was determined to be at least 5000 mg/kg/day for general systemic function, developmental/reproductive function, and estrogenic activity. Conclusion: Our results suggest that G1899 is not toxic to juveniles at doses of up to 5000 mg/kg/day.

• Clinical and Experimental Pediatrics
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• v.52 no.7
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• pp.824-831
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• 2009

Purpose : We aimed to investigate the efficacy of and functional recovery after intracerebral transplantation of different doses of mouse mesenchymal stem cells (mMSCs) in immature rat brain with hypoxic-ischemic encephalopathy (HIE). Methods : Postnatal 7-days-old Sprague-Dawley rats, which had undergone unilateral HI operation, were given stereotaxic intracerebral injections of either vehicle or mMSCs and then tested for locomotory activity in the 2nd, 4th, 6th, and 8th week of the stem cell injection. In the 8th week, Morris water maze test was performed to evaluate the learning and memory dysfunction for a week. Results : In the open field test, no differences were observed in the total distance/the total duration (F=0.412, P=0.745) among the 4 study groups. In the invisible-platform Morris water maze test, significant differences were observed in escape latency (F=380.319, P<0.01) among the 4 groups. The escape latency in the control group significantly differed from that in the high-dose mMSC and/or sham group on training days 2-5 (Scheffe's test, P<0.05) and became prominent with time progression (F=6.034, P<0.01). In spatial probe trial and visible-platform Morris water maze test, no significant improvement was observed in the rats that had undergone transplantation. Conclusion : Although the rats that received a high dose of mMSCs showed significant recovery in the learning-related behavioral test only, our data support that mMSCs may be used as a valuable source to improve outcome in HIE. Further study is necessary to identify the optimal dose that shows maximal efficacy for HIE treatment.

• Current Research on Agriculture and Life Sciences
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• v.3
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• pp.181-189
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• 1985

This study was conducted to determine the effect of the adrenal function on the reproductive organs in immature rats treated with PMS. Two hundred and ten female rats (Wistar-Imamichi albino rats) of 21 days old (body weight : $58.7{\pm}3.53g$) were disposed in the intact rat group (Int.-) and adrenalectomized rat group (Adx.-) and then each group was devided into 3 subgroups, such as control (-Cont.), PMS treated (-PMS) was administered subcutaneously with 25 IU PMS, and and PMS cortisol treated groups (-PMS+Corti.) with 25 IU PMS and $30.0{\mu}g$ cortisol on 5 th day (aged 26 days old) after adrenalectomy, while the control groups with physiological salt solution by the same way. The reprodutive organs were observed at 48, 54, 60, 66, 72, 78 and 84 hours after hormone treatments. The results obtained were as follows ; 1. The measurments of time average ovary weight in all treated groups were increased with the elapse of time after treatment, and the difference among the treatments was significant (p<0.01) in the all observation time. But the difference of those was not recognized in Int.-Cont. and Adx.-Cont. groups. In the multiple range test. ovary weight of adrenalectomized rat groups (Adx.-PMS and Adx.-PMS+Corti. groups) was significantly (p<0.05) lighter than those of intact rat groups (Int.-PMS and Int.-PMS+Corti. groups), and the effect of cortisol administration was not reconized. 2. The difference of uterus weight was significantly reconized (p<0.01) in all observation time. The weight in Int.-PMS and Int.-PMS+Corti. groups was heavier until 66 hours after treatment, but the values in the adrenalectomized Adx.-PMS and Adx.-PMS+Corti. groups were heavier after 72 hours. The multiple range test showed that the significant difference was not found between Int.-PMS and Int.-PMS+Corti. groups, and Adx.-PMS and Adx.-PMS+Corti. groups. 3. The adrenal weight was not significantly different among the compared groups.

• Korean Journal of Animal Reproduction
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• v.7 no.1
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• pp.30-40
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• 1983

This experiment was carried out to investigate the effects of unilateral and bilateral ovariectomy in immature rats on the weight of body, ovary, uterus and adrenal gland and the change of serum FSH and LH level. Ninty Sprague-Dawley female rats, 23${\pm}$2 days old, were divided into 3 groups with 30 heads per group; control, unilaterally and bilaterally ovariectomized group. Each group was subdivided into 6 groups according to 6 experimental periods; day 4, 8, 12, 16, 20, and 24 after operation. Five rats at every 4 days intervals were measured their body weights and sacrificed for the measurement of their ovarian, uterine and adrenal weights and at the same time blood samples were taken for the determination of serum FSH and LH level by radioimmunoassay. The following results were obtained: 1. Body weights in the unilaterally and bilaterally ovariectomized goups were higher than those of control groups during all experimental periods, even though there were no significant differences among the above 3 groups. 2. A significant hypertrophy of the remained ovary in the unilaterally ovariecto mized group was observed from day 16 till day 24 after operation. The ovarian weight; 22.1${\pm}$1.73mg, at day 16 in control group was smaller than the unilaterally ovariectomized group weighing 50.5${\pm}$8.45mg (p<0.01) and the ovarian weights, 75.9${\pm}$2.25mg and 63.3${\pm}$7.08mg ; at day 20 and 24 in unilaterally ovariectomized group were significantly larger than 29.1${\pm}$2.33mg and 26.3${\pm}$1.76mg in control group, respectively (p<0.01 and p<0.05). 3. The uterus of bilaterally ovariectomized group were remarkably atrophied from day 8 after operation as compared with those of control and unilaterally ovariectomized group. The uterine weight at day 24 was 96.7${\pm}$9.15mg for control group, 139.4${\pm}$1.73mg for unilaterally ovariectomized group and 21.7${\pm}$1.08mg for bilaterally ovariectomized group, respectively and there were significant differences among 3 groups (p<0.01). 4. A statistically significant increase ofthe weight of adrenal gland was observed at day 16 in the unilaterally ovariectomized group with 24.4${\pm}$2.58mg against 15.5${\pm}$3.09mg in control group and 13.9${\pm}$1.38mg in bilaterally ovariectomized group (p<0.05). The adrenal gland weight in unilaterally ovariectomized group with 24.7${\pm}$1.63mg at day 20 and 31.2${\pm}$1.62mg at day 24 increased significantly as compared with bilaterally ovariectomized group with 15.1${\pm}$13.11mg at day 20 and 15.6${\pm}$1.76mg at day 24. 5. Serum FSH level of unilaterally ovariectomized group increased remarkably up to 2.97${\pm}$0.37mIU/ml at day 4 after operaton and then decreased gradually. Serum FSH level of bilaterally ovariectomized group were higher than those of control group throughout all experimental periods. 6. Serum LH level ofunitelarally ovariectomized group with 3.17${\pm}$0.32mIU/iml at day 4 and 3.57${\pm}$0.58mIU/ml at day 24 increased noticeably more than those of control group with 1.79${\pm}$0.16 mIU/ml at day 4 and 2.17${\pm}$0.27mIU/ml at day 24 (p<0.05).

• Molecular & Cellular Toxicology
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• v.2 no.2
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• pp.106-113
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• 2006

Phthalate analogues are a plasticizer and solvent used in industry. Phthalates were classified in the category of "suspected" endocrine disruptors. The purpose of our study was to screen and elucidate the endocrine disrupting activity of seven phthalate analogues. E-screen assay was performed in MCF-7 human breast cancer cells with seven phthalate analogues. In this cell proliferation assay, benzyl butyl phthalate (BBP) and dibutyl phthalate (DBP) showed high estrogenic activity. Their relative proliferation efficiencies (RPE) were 109 and 106%, respectively. In vitro estrogen receptor (ER) binding assay, BBP, di-n-octyl phthalate (DOP) and dinonyl phthalate (DNP) showed weak relative binding affinity (RBA: 0.02%) compared to $17{\beta}-estradiol\;(E2)$ (RBA: 100%). In uterotrophic assay, E2 produced a significant increase, whereas four tested phthalate analogues had potential estrogenic effects in vitro did not increased in uterus weight in immature rats. From these results, we demonstrated that phthalate analogues exhibit weak estrogenic activity in vitro assays at high concentrations. Although phthalates induced an increase in MCF-7 cell proliferation by an estrogenic effect, they could not induce a uterus weight increase in vivo. From these, we may suggest that these phthalate analogues are easily metabolized to inactive forms in vivo. Further investigation in other in vitro and in vivo experimental systems might be required.