• 대한수의학회지
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• 제32권4호
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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.

• 한국발생생물학회지:발생과생식
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• 제21권4호
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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.

• 한국발생생물학회지:발생과생식
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• 제22권1호
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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.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2002년도 추계국제학술대회
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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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• 제22권3호
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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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• 제48권3호
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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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• 제52권7호
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• pp.824-831
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• 2009

목 적 : HIE의 치료법으로 줄기 세포가 대안으로 떠오르고 있다. mMSC가 성인 동물 모델에서의 뇌졸중 및 퇴행성 뇌질환에 유의한 기능 회복을 보인다는 보고가 많이 있으나 미성숙 동물 모델에서의 연구 보고는 거의 없는 상태이다. 이에 HIE가 유발된 미성숙뇌에 mMSC를 투여하여 기능 회복에 대한 효과를 평가하고자 본 연구를 시행하였다. 방 법 : 생후 7일된 수컷 Sprague-Dawley 흰쥐를 sham 대조군, 뇌 손상 대조군, 고용량 mMSC 이식군 및 저용량 mMSC 이식군으로 나누었으며 저산소 허혈 뇌 손상 유도 2주 후에 mMSC를 병변부 국소 이식을 시행하였다. 세포 이식 2, 4, 6 및 8주째에 개방장 시험을 시행하여 운동 기능 회복 정도를 평가하였고, 이후 1주일 동안 Morris 수중 미로 시험을 3개 부문으로 시행하여 학습 및 기억력 회복 정도를 평가하였다. 결 과 : 개방장 시험 결과 네 군간에서 통계적으로 유의한 차이는 없었다(F=0.412, P=0.745). 공간 획득 검사에서 네 군간 평균 탈출 시간에 서로 차이가 있었고(F=380.319, P<0.01), 고용량 mMSC 이식군 및 sham 대조군은 뇌 손상 대조군에 비해 검사 2일째부터 5일째까지 각각 평균 탈출 시간이 감소하였으며(P<0.05), 시간이 갈수록 더 유의하게 차이를 보였다(F=16.034, P<0.01). 참조 기억 검사에서는 네 군간 차이는 없었으며 시각 검사에서는 다섯번째 시행 검사에서만 고용량 mMSC 이식군과 뇌 손상 대조군간에 통계적으로 유의한 차이가 있었다(P<0.05). 결 론 : 일부 검사에서만 고용량 mMSC 이식의 효과가 뚜렷하였고 그 외의 검사에는 통계적으로 유의한 결과는 보이지는 않았으나 산술적인 호전을 보이는 것을 확인할 수 있었다. 향후 최적의 효과를 보이는 줄기 세포의 농도와 이식 시기를 결정하는 연구가 필요할 것으로 보이며 HIE에서 mMSC가 대안적인 치료 수단으로 이용될 수 있다고 생각된다.

• Current Research on Agriculture and Life Sciences
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• 제3권
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• pp.181-189
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• 1985

부신(副腎)의 기능(機能)이 생식기관(生殖器官)에 미치는 영향(影響)을 구명(究明)코자 21일령(日齡)의 암흰쥐(體重(체중): $58.7{\pm}3.53g$) 210마리를 정상(正常)흰쥐실험군(實驗群)(이하(以下) Int.-)과 부신척출실험군(副腎剔出實驗群)(이하(以下) Adx.-)으로 나누고, 각군(各群)을 다시 대조군(對照群)(이하(以下)-Cont.), PMS 투여군(投與群)(이하(以下) - PMS) 및 PMS와 cortisol의 병용투여군(이하(以下)-PMS+corti)의 3개군(個群)으로 나누어 35마리씩 배치(配置)한 다음 부신척출실험군(副腎剔出實驗群)에 대(對)하여 부신척출(副腎剔出)을 실시(實施)한 5일후(日後)(흰쥐 일령(日齡) : 26일(日))에 PMS투여군(投與群)에는 마리당 25IU의 PMS를, PMS와 Cortisol의 병용투여군에는 마리당 25IU의 PMS와 $30.0{\mu}g$의 Cortisol의 처리후(處理後) 48, 54, 60, 66, 72, 78 및 84시간(時間)에 5마리씩 도살(屠殺)하여 생식기능(生殖機能)의 중량(重量)을 측정(測定)하였다. 1. 난소(卵巢)의 중량(重量)은 모든 처리군(處理群)이 처리후(處理後) 기간(期間)이 경과(經過)할수록 증가(增加)하여 전관찰시간(全觀察時間)에서 비교군간(比較群間)에 고도(高度)의 유의성(有意性)(P<0.01)이 인정(認定)되었으나 대조군(對照群)인 Int.-Cont. 군(群)과 Adx.-Cont. 군(群)은 변화(變化)가 인정(認定)되지 않았다. 다중검정결과(多重檢定結果) 부신(副腎)을 척출(剔出)한 Adx.-PMS군(群)과 Adx.-PMS+Corti. 군(群)은 정상(正常)흰쥐 실험군(實驗群)인 Int.-PMS군(群)과 Int.-PMS+Corti. 군(群)에 비하여 유의(有意)(P<0.05)하게 낮은 값을 보였고, Cortisol 투여(投與)에 따른 효과(效果)는 인정(認定)되지 않았다. 2. 자궁(子宮)의 중량(重量)은 모든 관찰시간(觀察時間)에서 비교군간(比較群間)에 고도(高度)의 유의성(有意性)(P<0.01)이 인정(認定)되었는데, 처리후(處理後) 66시간(時間)까지는 정상(正常)흰쥐 실험군(實驗群)인 Int.-PMS군(群)과 Int.-PMS+Corti.군(群)이 높은 값을 보였고, 72시간(時間) 후(後)부터는 반대(反對)로 부신척출실험군(副腎剔出實驗群)인 Adx.-PMS군(群)과 Adx.-PMS+Corti.군(群)이 높은 값을 나타냈으며, 다중검정결과(多重檢定結果) Int.-PMS군(群)과 Int.-PMS-Corti.군(群), 그리고 Adx.-PMS군(群)과 Adx.-PMS군(群)과 Adx.-PMS+Corti.군(群) 상호간(相互間)에는 유의성(有意性)이 인정(認定)되지 않았다. 3. 정상(正常)흰쥐 실험군(實驗群)에서의 부신(副腎)의 중량(重量)은 Int.-PMS 군(群)에서 근소(僅少)하게 높은 값을 나타냈으나 비교군간(比較群間)에는 통계적(統計的)인 유의성(有意性)은 인정(認定)되지 않았고, 조직소견(組織所見)에서도 특기(特記)할 만한 변화(變化)를 인지(認知)할 수 없었다.

• 한국가축번식학회지
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• 제7권1호
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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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• 제2권2호
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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.