• Title/Summary/Keyword: Reproduction and developmental toxicity

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Effect of Ultraviolet-B Radiation Acclimation to Fresh Water Daphnia magna Simultaneously Exposed to Several Heavy Metals and UV-B Radiation (담수 물벼룩 Daphnia magna의 자외선 B 적응이 자외선과 중금속의 동시노출에 따른 독성반응에 미치는 영향)

  • Kim, Jung-Kon;Lee, Min-Jung;Oh, So-Rin;Choi, Kyung-Ho
    • Journal of Environmental Health Sciences
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    • v.33 no.2 s.95
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    • pp.123-131
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    • 2007
  • Many environmental contaminants including several metals, polycyclic aromatic hydrocarbons, and pharmaceuticals, have been identified to be phototoxic in the water environment. Concerns regarding photo-enhancement of toxicity of several environmental contaminants have been increasing because of the increased level of ultraviolet irradiation on the earth surface. However, there exist arguments that there might be certain defense mechanisms taking place in the aquatic ecosystem, which may include behavioral characteristics or genetic acclimation. This study was conducted to understand the potential responses of aquatic receptors to several phototoxic metals in the real environment, where long-term acclimation of such organisms to low dose UV-B may take place. For this purpose, water flea Daphnia magna was acclimated to environmentally relevant dose of UV-B (12 to $18uW/cm^2$) for >11 generations. The differences in developmental and life history characteristics, and toxicity responses were evaluated. Acclimation did not affect the daphnids' growth, longevity, and reproduction characteristics such as time to first brood, and brood size: After 21 d, survival of D. magna was not influenced by UV-B acclimation. When the number of young per female was compared. the daphnids acclimated for 11 generations tend to produce less number of neonates than the un-acclimated individuals but with no statistical significance (p>0.05). Four metals that were reported to be phototoxic elsewhere were employed in this evaluation, that include As, Cd. Cu, and Ni. UV-B level being applied in acclimation did increase the toxicity of Cd and Cu, significantly (p<0.05). However, the toxicities of As and Ni were not affected by irradiation of UV-B. Phototoxic responses were evaluated between the acclimated and the un-acclimated daphnids. For Cu, UV-B acclimation led to reduction of the photo-induced toxicity $(p\approx0.1)$ in daphnids. Non-acclimated Daphnia were affected by 50% at 4.18 ug/l Cu. but UV-B acclimated individuals exhibited $EC_{50}$ of 5.89 ug/l. With Cd, UV-B acclimation appeared to increase phototoxicity (p>0.05). With As and Ni, UV-B acclimation did not influence photo-induced toxicity. This observation may be in part explained by the type of reactive oxygen species that were generated by each metal. Similar to UV-B light, Cu is known to generate superoxide anion by acting as redox cycling toxicant. This is one of the first studies that employed_laboratory based UV-B acclimated test species for photoenhanced toxicity evaluation.

Effects of Alachlor and Endosulfan on the Survival and Malformation of Bombina orientalis Embryos (제초제 Alachlor과 살충제 Endosulfan이 무당개구리 (Bombina orientalis) 배아의 생존 및 기형유발에 미치는 영향)

  • 강한승;계명찬;이재성;윤용달;김문규
    • Korean Journal of Environmental Biology
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    • v.22 no.2
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    • pp.300-307
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    • 2004
  • The chloroacetanilide herbicide alachlor (2-chloro-2', 6'-diethyl-N-(methoxymethyl)-acetanilide) and organochlorine insecticide endosulfan (6, 7, 8, 9, 10, 10-hexachloro-l, 5, 5a, 6, 9, 9a-hexahydro-6, 9-methano-2, 3, 4-benzodioxathiepin-3-oxide)are the highly toxic agricultural chemicals. Bombina orientalis is one of the most common amphibians in the world and comprises a large proportion of their total number. B. orientalis spawns in the farming regions at Spring when the massive application of agricultural chemicals occurs. These chemicals in farmland may threaten the reproduction of this frog. Therefore, we examined the embryotoxic and survival effects of alachlor and endosulfan at various concentrations in B. orientalis embryos. The survival rates of embryos at 312h post fertilization treated with alachlor and endosulfan were decreased with concentration dependent manner. Also, developmental malformations appeared by alachlor and endosulfan in B. orientalis embryos. The malformations showed in order of frequency with bent trunk, tail dysplasia, bent tail, thick-set body and ventral blister in alachlor treated embryos. The exposure of endosulfan produced 7 types of severe external malformations with tail dysplasia, pectoral blister, bent trunk, bent tail, cephalic dysplasia, ventral blister, and thick-set body. Following exposure to alachlor and endosulfan the types of malformations were diverse, suggesting these chemicals target multiple events in embryonic and larval development in this species. These results suggested that alachlor and endosulfan were detrimental for survival and development of B. orientalis embryos.

Human Pluripotent Stem Cell-Derived Alveolar Epithelial Cells as a Tool to Assess Cytotoxicity of Particulate Matter and Cigarette Smoke Extract

  • Jung-Hyun Kim;Minje Kang;Ji-Hye Jung;Seung-Joon Lee;Seok-Ho Hong
    • Development and Reproduction
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    • v.26 no.4
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    • pp.155-163
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    • 2022
  • Human pluripotent stem cells (hPSCs) can give rise to a vast array of differentiated derivatives, which have gained great attention in the field of in vitro toxicity evaluation. We have previously demonstrated that hPSC-derived alveolar epithelial cells (AECs) are phenotypically and functionally similar to primary AECs and could be more biologically relevant alternatives for assessing the potential toxic materials including in fine dust and cigarette smoking. Therefore, in this study, we employed hPSC-AECs to evaluate their responses to exposure of various concentrations of diesel particulate matter (dPM), cigarette smoke extract (CSE) and nicotine for 48 hrs in terms of cell death, inflammation, and oxidative stress. We found that all of these toxic materials significantly upregulated the transcription of pro-inflammatory cytokines such as IL-1α, IL-β, IL-6, and TNF-α. Furthermore, the exposure of dPM (100 ㎍/mL) strongly induced upregulation of genes related with cell death, inflammation, and oxidative stress compared with other concentrations of CSE and nicotine. These results suggest that hPSC-AECs could be a robust in vitro platform to evaluate pulmotoxicity of various air pollutants and harmful chemicals.

Pharmacokinetics Characters and ADMET Analyses of Potently Pig Pheromonal Odorants (돼지 페로몬 성 냄새 분자들의 약물동력학적 특성과 ADMET 분석)

  • Choi, Kyung-Seob;Park, Chang-Sik;Sung, Nack-Do
    • Reproductive and Developmental Biology
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    • v.34 no.3
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    • pp.153-159
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    • 2010
  • The 34 potently pig pheromonal odorants (1-32, 5755 & 7113) through structure-based virtual screening and ligand-based virtual screening method were selected and their ADMET and pharmacokinetics characters were evaluated and discussed quantitatively. The pheromonal odorants were projected on the following pre-calculated models, Caco-2 cell permeability, blood-brain barrier permeation, hERG inhibition and volume-distribution. From the results of in silico study, it is found that an optimal compound (31) either penetrating or have a little ($P_{caco2}$=-8.143) for Caco-2 cell permeability, moderate penetrating ability ($P_{BBB}$=0.082) for blood-brain barrier permeation, the low QT prolongation ($P_{hERG}$=1.137) for the hERG $K^+$ channel inhibition, and low distribution into tissues ($P_{VD}$=-5.468) for volume-distribution. Therefore, it is predicted that the compound (31) a topical application may be preferable from these based foundings.

Prostaglandins Involving in Blastocyst Development through Calcium Mediated Signaling Pathway

  • Lee, Ja-Myong;Kwon, Hyuck-Chan;Lee, Seung-Jea;Cheon, Yong-Pil
    • Development and Reproduction
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    • v.15 no.1
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    • pp.17-24
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    • 2011
  • Lipid metabolites involved in cellular regulation as signaling mediators. Prostaglandins (PGs), metabolites of lipid are involved to pregnancy at the time of implantation but the functional roles of PGs on embryo development are still controversy and largely unknown. In previous report, the levels of $PGE_2$ and $PGF_{2a}$ at embryos of morula stage and blastocyst stage were explored (Cheon et al., 1998). In this study, the previous suggestion was confirmed and the possible downstream mediator of prostaglandin $E_2$ and prostaglandin $F_{2a}$ on the expansion and hatching of mouse embryo was examined. As expected, developmental rate of the blastocyst to expanded stage was a concentration-response curve that showed the highest expansion rate at 10 ${\mu}M$ $PGE_2$, but at 100 ${\mu}M$ $PGE_2$, the rate was decreased. In contrast to the $PGE_2$, $PGF_{2a}$ stimulated expansion without toxicity at highest concentration. Cotreatment of PGs with indomethacin overcame the inhibitory effects of indomethacin in expansion. Exogenous PGs also improved the development of expanded embryos to the hatching stage. Besides, PGs receptors' transcripts detected at blastocyst. $PGE_2$ was caused of calcium fluctuation in the blastocyst but $PGF_{2a}$ did not. The changes of intracellular calcium concentration were different between indomethacin pretreated embryos and non-treated embryos. Based on these results it is suggested that PGs work as paracrine and/or autocrine factors through calcium and the others which were not identified in this study.

Potential Importance of Proteomics in Research of Reproductive Biology (생식생물학에세 프로테오믹스의 응용)

  • Kim Ho-Seung;Yoon Yong-Dal
    • Development and Reproduction
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    • v.8 no.1
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    • pp.1-9
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    • 2004
  • The potential importance of proteomic approaches has been clearly demonstrated in other fields of human medical research, including liver and heart disease and certain forms of cancer. However, reproductive researches have been applied to proteomics poorly. Proteomics can be defined as the systematic analysis of proteins for their identity, quantity, and function. It could increase the predictability of early drug development and identify non-invasive biomarkers of toxicity or efficacy. Proteome analysis is most commonly accomplished by the combination of two-dimensional gel electrophoresis(2DE) and MALDI-TOF(matrix-assisted laser desorption ionization-time of flight) MS(mass spectrometry) or protein chip array and SELDI-TOF(surface-enhanced laser desorption ionization-time of flight) MS. In addition understanding the possessing knowledge of the developing biomarkers used to assess reproductive biology will also be essential components relevant to the topic of reproduction. The continued integration of proteomic and genomic data will have a fundamental impact on our understanding of the normal functioning of cells and organisms and will give insights into complex cellular processes and disease and provides new opportunities for the development of diagnostics and therapeutics. The challenge to researchers in the field of reproduction is to harness this new technology as well as others that are available to a greater extent than at present as they have considerable potential to greatly improve our understanding of the molecular aspects of reproduction both in health and disease.

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Effects of Manganese Exposure on the Testis Function and Serum Prolactin Concentration in Rat (망간 노출이 흰쥐의 정소기능과 혈청 프로락틴 농도에 미치는 영향)

  • Lee, Chae-Kwan
    • Development and Reproduction
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    • v.13 no.4
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    • pp.321-327
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    • 2009
  • This study aimed to examine the testis toxicities of metal compound, manganese (Mn), which may be generated as mist or fume in the industrial sites. As well as serum prolactin (PRL) concentration was analyzed because Mn accumulation in basal ganglia up-regulates serum PRL and hyperprolactinemia consecutively induces the testis toxicity. Male F344 rats were divided into the 4 groups (2 controls and 2 Mn treated groups, n=10) on the basis of the test condition (inhalation, Mn $1.5mg/m^3$ or not) and treatment period (for 4-weeks and 13-weeks). The treatment time was 6 hr. a day, 5 days a week for the whole body. Basic tests including changes in body weight, feed rate were observed. Blood and testis Mn concentration, and testis toxicity test such as the number and deformity test of sperm were also observed. Serum PRL level was analyzed by ELISA to certify the relationship between the Mn induced increase of the serum PRL level and sperm production. Blood and testis Mn concentrations were significantly and dose-dependently increased. Sperm count was decreased in Mn-treatment groups than control in a treatment time dependent manner. Morphological analysis of cauda epidydimal sperm showed that the frequencies of morphologically abnormal sperms such as bent tail and small head were increased in the both Mn-treatment groups than control. A significant increase in serum PRL levels was found in response to Mn treatment but it was not hyperprolactinemia range. These results suggest that treatment of Mn up-regulates the serum PRL concentration and induces the testis toxicity. The No Aversed Effect Level (NOAEL) of inhaled Mn on the male rat testis may be under the $1.5mg/m^3$.

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The Effect of Hyeonggaeyeongyotang Extract on the Fertility, Early Embryonic Development in Wistar rats by Oral Gavage Administration (형개련교탕(荊芥連翹湯) 추출물의 경구투여(經口投與)가 rat의 수태능(受胎能) 및 초기(初期) 배발생(胚發生)에 미치는 영향(影響))

  • Kim, Eun-Hee;Hwang, Sun-Yi;Kim, Sang-Chan;Jee, Seon-Young
    • Herbal Formula Science
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    • v.16 no.1
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    • pp.65-78
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    • 2008
  • Objectives : this study was to access the effect of Hyeonggaeyeongyotang water extracts, a polyherbal formula has been used as folk medicine, on the fertility and early embryonic development of male and female Wistar rats when administered by oral gavage. Methods : In male rats, Hyeonggaeyeongyotang extract were dosed 4 weeks before pairing and 2 weeks after mating including the mating periods up to termination after necropsy of the majority of the females. In female rats, they were dosed 2 weeks before pairing, and from Day 0 to Day 7 of gestation. This study was conducted in accordance with the recommendations of the KFDA Guideline [2005-60] for Detection of Toxicity to Reproduction for Medicinal Products. Results: 1. No Hyeonggaeyeongyotang extract treatment-related changes on the clinical signs and mortalities, the Food consumptions, the Body weights and gains were demonstrated in all dosed levels tested in this study except for 500ml/kg-dosing male group in which a significant(p<0.05) increase of body gains was detected during day 0-7 after dosing. 2. No Hyeonggaeyeongyotang extract treatment-related changes on the pre-coital intervals, the estrus cycles, the mating index, conception rate and fertility index were demonstrated in all dosed levels tested in this study. 3. No Hyeonggaeyeongyotang extract treatment-related gross findings on reproductive organs, the weights of reproductive organs, histopathological findings on reproductive organs, the corpora lutea number, implantation site number, live fetus number, number of resorpted embryo and pre-and post-implatation loss were demonstrated in all dosed levels tested in this study. Conclusions : Base on the results, it is considered that the NOAEL (No-Observed-Adverse-Effect Level) for fertility and early embryonic development toxicity of Hyeonggaeyeongyotang extract was under 2000ml/kg/day in Wistar male and female rats because there no treatment-related changes on the fertility and early embryonic developmental index were demonstrated in all dosed levels tested.

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Initial Risk Assessment of Acetanilide with Respect to Human Health (아세트아닐리드의 초기 인체위해성 평가)

  • Lee, Su-Rae;Park, Seon-Ju;Lee, Mi-Kyung;Nam, U-Kyung;Chung, Sun-Hwa;Seog, Geum-Su;Park, Kwang-Sik;Kim, Kyun;Kim, Yong-Hwa
    • Environmental Analysis Health and Toxicology
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    • v.15 no.1_2
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    • pp.31-37
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    • 2000
  • Acetanilide may be released into the environment through air and wastewater from its production and use sites and exposed to human. Acetanilide is known to produce an analgesic effect and may pose adverse effects on human health by overly exposure. According to the EUSES system, acetanilide showed a high MOS (Margin of safety) value exceeding 6$\times$10$^4$ on a regional exposure, which is safe enough for public health. Whereas the lowest MOS value in dermal exposure was estimated as 3$\times$10$^{-4}$ on a local basis (workplace), the risk could be partly counteracted by taking preventive measures such as using mask and globes and good ventilation in the work places. Acetanilide may pose a potential risk for workers by dust inhalation. For the sake of health protection in the work places, additional data should be accumulated with respect to repeated dose toxicity, reproduction toxicity and developmental toxicity, etc. It is, therefore, recommended that acetanilide should be a candidate for further work to supplement the lacking data until it is proved to be safe in the occupational health aspects.

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Ameliorating Effect of Selenium against Arsenic Induced Male Reproductive Toxicity in Rats

  • Jalaludeen, Abdulkadhar Mohamed;Lee, Ran;Lee, Won Young;Kim, Dong Hoon;Song, Hyuk
    • Reproductive and Developmental Biology
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    • v.38 no.3
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    • pp.107-114
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    • 2014
  • Oral exposure of humans by excess amounts of arsenic may cause disturbances of the reproductive system. In the present study, such exposure was modelled in rats, with the support of sperm principal parameters and histopathological observations. Male Sprague-Dawley rats were randomly divided into three groups where the group I was served as a normal control, group II was received sodium meta-arsenite as arsenic (10 mg/kg b.w/day) and a combination of sodium meta-arsenite and sodium selenite (3 mg/kg b.w/day) in group III. After 6 weeks, there was no significant change in testis weight and in total motility of all the three experimental groups, whereas, rapid moving spermatozoa, moderately moving spermatozoa and slow moving spermatozoa were significantly decreased in arsenic treated rats as compared to control rats. The other sperm principal parameters like progressiveness, average path velocity, straightness linear velocity (VSL), curvilinear velocity (VCL), straightness, linearity sperm head elongation ratio, area, linearity amplitude of lateral head department (ALH) and beat cross frequency (BCF) were found to be reduced in arsenic intoxicated rats. These results are not correlated with the histological studies. On oral administration of selenium ameliorated the adverse effects of arsenic as compared to arsenic alone treated rats. Our findings clearly demonstrate that administration of selenium could prevent some of the deleterious effects of arsenic in the testis.