난관수종액이 생쥐 체외수정과 배아 발달에 미치는 영향

양회생(Hoe Saeng Yang) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.7

Objective : To ascertain if hydrosalpinges are associated with reduced pregnancy rates and increased pregnancy loss after IVF-ET, a study was conducted. Increased volume and leakage of hydrosalpinx fluid may exert negative effects on follicular development and embryo quality and/or render the uterine environment hostile to embryogenesis. This study was undertaken to examine the effect of hydrosalpinx fluid an mouse embryogenesis in vitro. Methods :The study was designed by comparison of mouse embryo blastulation rate in media containing increasing concentrations of hydrosalpinx fluid. In vitro fertilization rate and the development of one-, two-, four-cell mouse embryos in medium containing 0% (Control), 0.3%, 0.6%, 0.9%, 5%, 10% and 20% of human hydrosalpinx fluid-containing media was observed. Results :In vitro fertilization and culture of mouse embryo at 0% (control), 0.3%, 0.6%, 0.9%, 5%, 10%, 20% hydrosalpinx fluid concentrations demonstrated significantly 1ower blastulation rate at each level compared with the controls (p<0.05). In vivo fertilization and culture of embryo at the same increasing concentration of hydrosalinx fluid showed the same results (p<0.05). And the difference of each embryo development (zygote, 2cell, 4cell) was not significant. Conclusion :Hydrosalpinx fluid is highly embryotoxic. Procedures such as, salpingectomy ar proximal tubal occlusion to circumvent the passage of hydrosalpinx fluid into the uterine cavity may have beneficial effects on the developmental environment for embryos in vivo.

착상후 배자배양시스템을 이용한 생식독성연구 : Azole계 화학물질의 흰쥐 배자독성과 알코올 병용투여의 영향 mbryotoxicity of azole compounds and combination effect with alcohol

한순영,박귀례,홍진태,박기숙,김형식,오세동,최윤진,표명윤,장성재 식품의약품안전청 1997 식품의약품안전청 연보 Vol.1 No.-

Azole계 화학물질중 담배, 담배연기, 커피향등에 포함된 성분으로 보고된 benzothiazole유도체, benzoxanolem유초체, carbazole등의 최기형성을 in viro에서 검색하고, 같이 섭취하기 쉬운 알코올과 병용할 때 태자에 미치는 영향을 알아보고자 하였다.외부물질에 의한 배지의 신체 전반적 성장 발달에 대한 영향과 기형유발릉ㄹ 관찰할 수 있는 착상후 배자배양법을 사용, 임신 9.5일령의Wistar 흰쥐의착상우 배자에실험무질을 처리하고 48시간 배양한 후 형태 이상 유 ·무를 검색하고, 배자 각 기관의 성장 및 발달을 Van Maele-Fabry법에 따라 관찰하고 단백질함량을 측정 하였다. Benzothiazole (10-"~10-'M), 2-aminobenzothiaBole (10-"~5 f 10-"M), thiazole (10-"~10-'M), 2,5-dimethylbenzoxazole (10-"~10-"M), carbaBole (10-"~10-'M) 처리애 의하여 시험물질에 따라 짤현 부위 및 정로의 차이는 있으나 배자의 탈달 띤 성장의 지연을 유발하였는데, beRzothi,azole은 otic system, optic system 및 semite발달에, 2-aminobenzothiazole은 yolk sac diameter, head length, yotlt sac circulatory system에,thiazole은 yolk sac circulatory system, midbrain, otic system, optic system 및 forelimbfl , 2, S-djmethylbenzoxazole은 otic system, optic system 및 midbrain 발달에 , carbazole은 뇌발달에 특히 영향을 주었으며, t얀리 score의 유의적인 감소와 꼬리부분의 형태이상이 공통적으로 관찰되었다. Ethanol 처레로 심장, 뇌,otic, opt곯 3ystem, mandibular process 등의 발달에 영항을 미쳤고, 착상후 배자에 alcohol과 azole화합물을 복합처리할 메에 배자 발달 및 실장 지연의 심화경향이 관찰되었다. 따라서 담배, 커피등께 함유된 azole화합물의 양이 미량플지라도 배자독성 및 최기형성의 가능성과 알코올과 동시에 섭취할 때 배자독성증가의 가능성을 배제할 수는 없는 것으로 생각된다. Tobacco and coffee contain many compounds including azole group compounds, but a tie iBformatioB is available iri thesingle or the combinati㉠n with ethrandcultured for 48 h with diiferent doses of asole compounds [bengothiaBole & carbaBole (10-"~10--aBOM), 2-amino-benzothiazole (10-"~5×10-"M), thiazole (10-"~ 10-"H[), 2,5-dimethylbenzoxaBole (10-'-10-'M)] alone or the combination with 0.3% ethanol. Morphologicat ct.anges were determined uader mi.croscope for evaluation of e81bryo deITelopment and scored by the method of Van Maele-Fabrf. Atl ofcompound tested caused significant reduction of total score and abnormal tail development. In addition,benzothiazote, thiazole aBd 2,5-dimethylbenzoxazole inhibited otic and optic development. Thiasole aad2-nminobenpothiazole also inhibited the development of yollt sac circulatory system, yolk sack and headvelopment. Ethanol also cauE,ed reduction of heart, brain, otic, optic a.nd mandibular developraent. The embryotoxicity by the combirlation:-treatment of azole and ethanol was much greater than those by eachchemical alone. These data 1:uggest that some of azole compounds pi·esented in tobacco or/and coffeearoma may cause embryotoxicity, and the addition of ethanol increased their toxicity in cultured rat em-bryos.

Embryotoxic effects of DA-125, a new anthracycline anticancer agent, in rats

정문구,김종춘,Chung, Moon-koo,Kim, Jong-choon The Korean Society of Veterinary Science 1994 大韓獸醫學會誌 Vol.34 No.1

DA-125는 새로운 안트라사이클린계 항암성 항생제로서 아드리아마이신의 유도체이다. Sprague-Dawley 랫트를 이용하여 DA-125의 배아 및 태자독성발현능력을 조사하였다. 교미확인(정충확인일=0일)된 120마리의 랫트를 4개군으로 나눈후 0, 0.1, 0.3 및 1.0mg/kg의 용량으로 임신 7일 부터 임신 17일까지 1일 1회 연속 정맥투여 하였으며 임신 20일째에 제왕절개를 하여 태자를 적출하였다. 1mg/kg 투여군에서는 모동물의 사료섭취량의 감소, 체중감소 및 비장중량의 감소와 배아 흡수율의 증가 및 태자체중의 감소가 관찰되었다. 또한 여러가지 종류의 외표, 내부장기 및 골격기형들이 각각 11.9, 41.8 및 14.5%의 빈도로 출현했다. 그중 특이 기형소견으로는 뇌탈출증, 복벽파열, 외측 및 제3뇌실의 확장, 늑골유착 등을 들 수 있다. 0.1 및 0.3mg/kg 투여군에서는 어떠한 배아 및 태자 독성증상도 나타나지 않았다. 이상의 결과에서 DA-125는 랫트에 있어서 경미한 모독성 용량에서 배아 및 태자독성효과를 나타냄을 알 수 있었다. DA-125 is a new anthracycline antitumor antibiotic, which is derived from adriamycin. The potential of DA-125 to induce embryotoxicity was evaluated in the Sprague-Dawley rats. One hundred twenty naturally mated SD rats(sperm in vaginal lavage=day 0) were distributed among three treated groups and a control group. DA-125 was administered intravenously at dose levels of 0. 0.1, 0.3 and 1.0mg/ kg/day. Dams were treated from day 7 to 17 of gestation and were subjected to the caesarean section on day 20. At 1 mg/kg, reduced food intake, reduced body weight and decreased weight of spleen were observed in dams. An increase in the resorption rate and a reduction in the fetal weight were also found. In addition, various types of external, visceral and skeletal malformations occurred at an incidence of 11.9, 41.8 and 14.5%, respectively. Characteristic malformations include exencephalia, gastroschisis, cleft lip, dilatation of lateral and 3rd ventricle, fused ribs, among others. There were no signs of maternal toxicity or embryotoxicity at 0.1 and 0.3mg/kg. The results show that the test agent DA-125 is embryotoxic at maternally subtoxic dose in rats.

Effects of Phenobarbital Pretreatment on Ethyl Carbamate-induced Embryotoxicity in Rats

Chung, Moon-Koo,Jiang, Cheng-Zhe,Kim, Jong-Choon,Yun, Hyo-In,Han, Sang-Seop,Roh, Jung-Koo Korean Society of ToxicologyKorea Environmental Mu 1997 Toxicological Research Vol.13 No.1

Ethyl carbamate (EC) is a potent teratogen in rodents and is present at low concentration in fermented foods and alcohol beverages. It has been well hypothesized that some metabolic products are responsible for the teratogenic effects of the compound. In the present study, the effects of phenobarbital (PB) on EC-induced embryotoxicity were investigated in SD rats. Six groups were constructed: EC 300 (EC 300 mg/kg/day), EC 600 (EC 600 mg/kg/day), EC 600+PB (EC 600 mg/kg/day and PB 80 mg/kg/day), PB (PB 80 mg/kg/day), DR (dietary restriction, 8 g/day/rat) and a control group. Rats of the EC 600+PB group were pretreated with phenobarbital intraperitoneally for three days to induce cytochrome P450 enzymes, followed by oral administration of EC for two consecutive days. The incidence of fetal deaths in the EC 600+PB group was higher than that of the EC 600 group(42.7 vs. 14.3%). The incidence of fetal realformations in the EC 600+PB group was higher than that of the EC 600 group (external; 7.0 vs. 4.1%, visceral; 31.4 vs. 11.3%, skeletal; 11.1 vs. 6.5%). There was no embryotoxicity in the control, EC 300, PB and DR groups. These results show that the pretreatment with phenobarbital augments EC-induced embryotoxicity in rats, indicating an evidence that metabolic activation by cytochrome P450 may be the major pathway of EC to its embryotoxic forms.

Impact of Nicotine Exposure on Hair Cell Toxicity and Embryotoxicity During Zebrafish Development

유명훈,나윤찬,박세미,권순일,임기정,채성원,정학현,최준 대한이비인후과학회 2018 Clinical and Experimental Otorhinolaryngology Vol.11 No.2

Objectives. Nicotine has various adverse effects including negative impacts associated with maternal exposure. In the current study, we examined nicotine-induced damage of hair cells and embryotoxicity during zebrafish development. Methods. Zebrafish embryos were exposed to nicotine at several concentrations (5, 10, 20, and 40 μM) and embryotoxicity were evaluated at 72 hours, including hatching rate, mortality, teratogenicity rate, and heart rate. Hair cells within the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) neuromasts were identified at 120 hours. Apoptosis and mitochondrial damage of hair cells were analyzed using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling) and DASPEI (2-[4-(dimethylamino)styryl]-N-ethylpyridinium iodide) assays, respectively, and changes of ultrastructure were observed by scanning electron microscopy. Results. The control group without nicotine appeared normal with overall mortality and teratogenicity rate <5%. The hatching rate and mortality rate was not significantly different according to nicotine concentration (n=400 each). The abnormal morphology rate (n=400) increased and heart rate (n=150) decreased with increasing nicotine concentration (P<0.05). Nicotine-induced hair cell damage significantly increased as nicotine concentration increased. A significantly greater number of TUNEL-positive cells (P<0.01) and markedly smaller DASPEI area (P<0.01) were shown as nicotine concentration increased. Conclusion. The current results suggest that nicotine induces dose-dependent hair cell toxicity in embryos by promoting apoptosis and mitochondrial and structural damage.

Embryotoxic and Teratogenic Effects of Tartrazine in Rats

Hashem, Mohamed Mohammed,Abd-Elhakim, Yasmina Mohammed,Abo-EL-Sooud, Khaled,Eleiwa, Mona M.E. Korean Society of ToxicologyKorea Environmental Mu 2019 Toxicological Research Vol.35 No.1

Tartrazine (TAZ) is one of the most commonly used artificial dyes for foods and drugs. We determined the effect of TAZ on fetal development by examining morphological, visceral, and skeletal malformations in rat fetuses following daily oral administration of TAZ to pregnant Wistar rats at the 6th-15th day of gestation. TAZ at 0.45 and 4.5 mg/kg induced 6.0 and 7.1% fetal resorptions, as well as 10.0 and 10.5% fetal mortality, respectively. Fetal body weight and length were significantly lower in the groups treated with TAZ at 0.45 ($3.97{\pm}0.21g$ and $27.3{\pm}0.54mm$, respectively) and 4.5 mg/kg ($3.48{\pm}0.15g$ and $23.22{\pm}1.02mm$, respectively) than in the control group ($4.0{\pm}0.15g$ and $30.01{\pm}0.42mm$, respectively). TAZ at 0.45 and 4.5 mg/kg induced hepatic damage (20 and 33.3%, respectively), dark brown pigmentation due to hemosiderin in the splenic parenchyma (16.7 and 21.7%, respectively), as well as destructed and necrotic renal tubules (16.7 and 26.7%, respectively) in the fetuses. Moreover, TAZ at 0.45 and 4.5 mg/kg caused one or more missing coccygeal vertebrae (20 and 40%, respectively), missing sternebrae (6 and 10%, respectively), missing hind limbs (24 and 4%, respectively), and irregular ribs (16 and 20, respectively) in the fetuses. We concluded that TAZ has embryotoxic and teratogenic potentials in rats.

Embryotoxicity and Toxicokinetics of the Antimalarial Artesunate in Rats

Chung, Moon-Koo,Yu, Wook-Joon,Lee, Jin-Soo,Lee, Jong-Hwa Korean Society of ToxicologyKorea Environmental Mu 2013 Toxicological Research Vol.29 No.1

This study was conducted to investigate the potential embryo-fetal toxicity and toxicokinetics of the antimalarial agent artesunate (ARTS) in Sprague-Dawley rats. Pregnant rats were administered ARTS daily from gestational day 6~15 via oral gavage, at test doses of 0, 2, 4, or 8 mg/kg (22 females per group). The fetuses were examined for external, visceral, and skeletal abnormalities on gestational day 20. With regard to the dams, there were no deaths, treatment-related clinical signs, changes in body weight, or food intake in any of the treatment groups. There were no treatment-related gross findings at necropsy in any treatment group. In the 8 mg/kg group, there was a decrease in gravid uterine weight and in the weight of female fetuses. There was also an increase in fetal deaths (primarily late resorptions) and an increase in post-implantation losses (37%) at 8 mg/kg. An increase in the incidence of visceral and skeletal variations at 4 and 8 mg/kg was observed. These defects included minor changes in the appearance of the kidney and thymus, as well as absent ribs or thoracic vertebrae. Toxicokinetics were assessed in a parallel study, using 4 mated females per group. Using liquid chromatography-mass spectrometry (LC-MS) analysis, the concentration of ARTS and its metabolite dihydroartemisinin (DHA) were quantified in plasma from rats on gestational days 5, 6, 10, and 15. Amniotic fluid was assayed for ARTS and DHA on gestational day 15. There was evidence of rapid conversion of ARTS to the metabolite DHA in maternal plasma, since ARTS could not be consistently detected in plasma at the three doses tested. ARTS and DHA were not detected in amniotic fluid at gestational day 15, indicating limited placental transfer of the two agents. The embryo-fetal no-observable-adverse-effect level (NOAEL) of the test item was considered to be 8 mg/kg/day for dams, and 2 mg/kg/day for embryo-fetal development.

Embryotoxic and Teratogenic Effects of Tartrazine in Rats

Mohamed Mohammed Hashem,Yasmina Mohammed Abd-Elhakim,Khaled Abo-EL-Sooud,Mona M. E. Eleiwa 한국독성학회 2019 Toxicological Research Vol.35 No.1

Tartrazine (TAZ) is one of the most commonly used artificial dyes for foods and drugs. We determined the effect of TAZ on fetal development by examining morphological, visceral, and skeletal malformations in rat fetuses following daily oral administration of TAZ to pregnant Wistar rats at the 6th-15th day of gestation. TAZ at 0.45 and 4.5 mg/kg induced 6.0 and 7.1% fetal resorptions, as well as 10.0 and 10.5% fetal mortality, respectively. Fetal body weight and length were significantly lower in the groups treated with TAZ at 0.45 (3.97 ± 0.21 g and 27.3 ± 0.54 mm, respectively) and 4.5 mg/kg (3.48 ± 0.15 g and 23.22 ± 1.02 mm, respectively) than in the control group (4.0 ± 0.15 g and 30.01 ± 0.42 mm, respectively). TAZ at 0.45 and 4.5 mg/kg induced hepatic damage (20 and 33.3%, respectively), dark brown pigmentation due to hemosiderin in the splenic parenchyma (16.7 and 21.7%, respectively), as well as destructed and necrotic renal tubules (16.7 and 26.7%, respectively) in the fetuses. Moreover, TAZ at 0.45 and 4.5 mg/kg caused one or more missing coccygeal vertebrae (20 and 40%, respectively), missing sternebrae (6 and 10%, respectively), missing hind limbs (24 and 4%, espectively), and irregular ribs (16 and 20, respectively) in the fetuses. We concluded that TAZ has embryotoxic and teratogenic potentials in rats.

Study on Embryotoxicity of Arsanilic acid Using Mouse Embryonic Stem Cells(초)

( Eun Joo Kim ),( Sang Hee Jeong ),( Young Joo Lee ),( Eun Ju Park ),( Hyo Shuk Shin ),( Joon Hyoung Cho ),( Jeong Woo Kang ),( Young Il Park ),( Seong Wan Son ) 한국동물실험대체법학회 2009 한국동물실험대체법학회 학술대회집 Vol.2009 No.3

Embryotoxicity and Toxicokinetics of the Antimalarial Artesunate in Rats

정문구,유욱준,이진수,이종화 한국독성학회 2013 Toxicological Research Vol.29 No.1

This study was conducted to investigate the potential embryo-fetal toxicity and toxicokinetics of the antimalarial agent artesunate (ARTS) in Sprague-Dawley rats. Pregnant rats were administered ARTS daily from gestational day 6~15 via oral gavage, at test doses of 0, 2, 4, or 8 mg/kg (22 females per group). The fetuses were examined for external, visceral, and skeletal abnormalities on gestational day 20. With regard to the dams, there were no deaths, treatment-related clinical signs, changes in body weight, or food intake in any of the treatment groups. There were no treatment-related gross findings at necropsy in any treatment group. In the 8 mg/kg group, there was a decrease in gravid uterine weight and in the weight of female fetuses. There was also an increase in fetal deaths (primarily late resorptions) and an increase in post-implantation losses (37%) at 8 mg/kg. An increase in the incidence of visceral and skeletal variations at 4 and 8 mg/kg was observed. These defects included minor changes in the appearance of the kidney and thymus, as well as absent ribs or thoracic vertebrae. Toxicokinetics were assessed in a parallel study, using 4 mated females per group. Using liquid chromatography-mass spectrometry (LC-MS) analysis, the concentration of ARTS and its metabolite dihydroartemisinin (DHA) were quantified in plasma from rats on gestational days 5, 6, 10, and 15. Amniotic fluid was assayed for ARTS and DHA on gestational day 15. There was evidence of rapid conversion of ARTS to the metabolite DHA in maternal plasma, since ARTS could not be consistently detected in plasma at the three doses tested. ARTS and DHA were not detected in amniotic fluid at gestational day 15, indicating limited placental transfer of the two agents. The embryofetal no-observable-adverse-effect level (NOAEL) of the test item was considered to be 8 mg/kg/day for dams, and 2 mg/kg/day for embryo-fetal development.