• Development and Reproduction
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• v.10 no.4
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• pp.255-261
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• 2006

Although some phytoes rogens might have beneficiary rather than adverse effects, most endocrine disrupting compounds(EDCs) are considered to be harmful to human and wildlife health through interfering the endocrine system. Previously we found that prepubertal exposure to genistein(GS), a well-known isoflavone phytoestrogen, could activate the reproductive system of immature female rats resulting precocious puberty. Interestingly, di(2-ethyl hexyl) phthalate(DEHP) exposure brought inverse result, a delayed puberty, in the same experimental regimen. In this study, we examined whether prepubertal exposure to GS or DEHP affect the gene expressions of estrogen receptors($ER\;{\alpha}$ and $ER\;{\beta}$) and LH receptor(LHR) which represent the maturational status of ovary and uterus in immature rats. GS (100 mg/kg/day) was administered daily from postnatal day 25 to the day when the first vaginal opening(VO) was observed, and the animals were sacrificed on the next day(day 32). Similarly, DEHP(l00 mg/kg/day) was administered daily from postnatal day 25 through the day when the first V.O. in control group was observed, and the animals were sacrificed on the next day(day 36). To determine the transcriptional changes in the hormone receptors, total RNAs were extracted from ovary and uterus and were applied to semi-quantitative reverse transcription polymerase chain reaction(RT-PCR). In the GS group, the transcriptional activities of $ER\;{\alpha}$, $ER\;{\beta}$ and LHR in uterus and LHR in ovary were significantly increased when compared to those of control group. In the DEHP group, the transcriptional activities of all the hormone receptors measured were significantly lowered when compared to those of control group. These alteration of the reproductive hormone receptor expressions in ovary and uterus might be represent the phenotypic aspects(secondary sexual characteristics) such as tissue weights and reproductive hormone levels during perinatal period in immature female rats.

• Development and Reproduction
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• v.15 no.2
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• pp.159-166
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• 2011

Simazine (6-chloro-N,N'-diethyl-1,3,5-triazine-2,4-diamine) is a triazine herbicide that has been applied worldwide including Korea for agricultural purposes. Simazine is the second most commonly detected pesticide in surfaceand ground-water in the United States, Europe and Australia. It has been shown that simazine is a potent endocrine disruptor in wildlife and laboratory animals. Although many endocrine disruptors can induce apoptosis in various types of cells, the effects of simazine on apoptosis and on the expression of Bcl-2 family genes are not known. Also it is unknown the effect of simazine on the expression of steroidogenesis-regulating genes in testicular cells. In this study, we investigated the effect of simazine on the expression levels of apoptosis- and steroidogenesis-regulating genes in testicular cells. We found that a low concentration of simazine can alter the mRNA expression levels of steroidogenesis-related genes and Bcl-2 family genes in mouse Sertoli cells and rat Leydig cells. Thus, our results suggest that simazine can disturb normal testicular development and reproductive function by altering the expression of genes that are critical for the regulation of apoptosis and steroidogenesis.

• Korean Journal of Clinical Laboratory Science
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• v.51 no.1
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• pp.86-92
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• 2019

Di-ethylhexyl phthalate (DEHP) is an environmental contaminant that is used as a plasticizer. Endometriosis is a complex disease with an unknown etiology that is believed to be associated with exposure to DEHP. The present study examined the potential toxicity of DEHP by exposing endometrial adenocarcinoma cells (Ishikawa cells) to DEHP. In the experiments, the cells were treated with stepwise DEHP concentrations (0, 0.01, 0.1, 1, and $5{\mu}M$) for different exposure times (24, 48, and 72 h). When the relationship between the resulting survival rate of the cells and initial inflammation was examined, the cell viability, expression of $TNF-{\alpha}$, an inflammatory mediator, and the expression of MMP-9, an ECM degradation protein, were increased remarkably when the cells were exposed to $5{\mu}M$ DEHP for 48 and 72 hours. These results suggest that the exposure of Ishikawa cells to certain concentrations of DEHP, estrogen mimics, may cause time-dependent toxicity that affects the cell viability and inflammation, implying a potential role in the etiology of endometriosis. Further research on the effects of endocrine disruptors on the pathogenesis of endometriosis may reveal strategies to prevent this disease.

• Toxicological Research
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• v.21 no.2
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• pp.161-165
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• 2005

Bisphenol A (SPA), a environmental endocrine disruptor, is considered to bind to estrogen receptors and to regulate the expressions of estrogen responsive genes. This study was to evaluate the effect of SPA administration on body weight, sex ratio and litter size on 18 days in prenatal periods, the effect of reproductive organ weight and blood hematological values on 24 days postpartum in pregnant mice. The female mice was administrated to low doses of SPA (0, 0.05, 0.5 and 5.0 mg/kg B.W.) by intraperitoneal injection in gestation days $0\~15$ with 5 times at 3 days interval. The maternal body weight, litter size and sex ratios were similar to in all experimental groups, but body weights of male and female offspring was significantly lower in 5.0mg SPA group when compared to any other groups (P<0.05). No treatment-related effects on body weight, ovary weight and blood hematological values were observed in dams on 24 days after delivery. The uterine weight in 5.0mg SPA group was slightly higher than those of any other groups, but not significantly difference. The histological evaluation of ovary in dam mice on 24 days after dilivery was not difference in all experimental groups, but the endometriosis of uterus in dam mice were significantly increased in 0.5mg SPA group when compared to control group. These results indicates that low concentration of SPA should not be considered as a selective reproductive toxicant.

• Korean Journal of Food Science and Technology
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• v.42 no.3
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• pp.277-280
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• 2010

Bisphenol A (BPA) is an endocrine disruptor frequently used in food containers, including epoxy resin and polycarbonates. BPA concentrations were monitored by high performance liquid chromatography (HPLC) under photosensitization of riboflavin (RF), methylene blue (MB), rose bengal (RB), or titanium dioxide ($TiO_2$) and the involvement of singlet oxygen was determined using sodium azide ($NaN_3$). The stability of BPA decreased significantly in the order of RF, RB, and MB photosensitization (p<0.05), while the concentration of BPA in samples with $TiO_2$ was not significantly different from that of control samples without photosensitizers under light (p>0.05). The stability of BPA decreased in an MB concentration-dependent manner and increased as the concentration of added $NaN_3$ increased, implying that singlet oxygen was involved in the photodegradation of BPA during MB photosensitization. The results of this study may help control the BPA content in foods or the environments using photosensitized oxidation and visible light irradiation.

• Journal of Environmental Health Sciences
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• v.29 no.4
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• pp.27-34
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• 2003

Bisphenol A is used in the manufacture of epoxy, polycarbonate, and corrosion-resistant unsaturated polyester-styrene resins required for food packaging materials in industrial processing. Some reports indicated the possibility of harmful effects on rats. In this study was used a method for the determination of bisphenol A in blood according to the OSHA High Performance Liquid Chromatography (HPLC) guideline. The method involved blood extraction using methylene chloride. And it was evaluated developmental and teratogenic effects in pregnant rats and second generation. The results obtained were as follows. There was a significant increase in the body weights and treated groups F1 female in liver, spleen, kidney, but according to dose-response. F1 female rat's relative body weight and absolute body weight are not different. There was a significant increase liver, spleen, kidney organ weight and reproductive organ weight epididymis, prostate gland in F1 male rats. There was a proestrous in pregnant rat, group 200 $\mu\textrm{g}$/kg, 2000 $\mu\textrm{g}$/kg, 20,000 $\mu\textrm{g}$/kg. The effect on rat treated with bisphenol A decrease organ weight and reproductive organ weight. Identification and quantitation were performed with using HPLC C18 column and using at retention time 5.5 min. The results of the detection of bisphenol A were at 20,000 $\mu\textrm{g}$/kg in average 1 $\mu\textrm{g}$/ml, 200 $\mu\textrm{g}$/kg average in 0.9 $\mu\textrm{g}$/ml blood samples. From those results, it could be concluded that the effects of pregnant rat and second generation(F1) by bisphenol A treatment during lactational period were estrogenic and bisphenol A was remained in serum at low level.

• Applied Chemistry for Engineering
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• v.27 no.3
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• pp.259-264
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• 2016

In this study, we applied six different norbornene dialkyl esters as a plasticizer to an isoprene rubber (IR) and evaluated replaceability of DEHP which is an endocrine disruptor. IR test sheets were prepared by blending IR, norbornene dialkyl ester, vulcanizing agent, etc. and processing properties of the IR were evaluated by measuring Toque, scorch time, cure time and mooney viscosity. Mechanical properties of IR test sheet including hardness, tensile strength, 100% modulus and elongation were also measured and the physical properties of norbornene dialkyl ester applied as a plasticizer were compared to those using DEHN. Both the maximum and minimum toque for the norbornene dialkyl ester as a plasticizer were similar to those of using DEHP. In addition, the scorch and cure time of the former were slightly longer than those of the latter. The mooney viscosity for the case of DEHN was slightly lower than that of the latter. DEHN was also superior to DEHP in terms of processing. The hardness and thermal properties of all IR test sheets were measured to be similar to each other. The linear alkyl chain of norbornene compounds also exhibited good tensile characteristics.

• Korean Journal of Environmental Biology
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• v.21 no.2
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• pp.208-215
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• 2003

Bisphenol A (4,4'-isopropylidenediphenol, $C^{15}H_{16}O_{2}$) is the monomer used in the manufacture of polycarbonate. Polycarbonate, in turn, is used in a wide array of plastic products, with new applications continuously being developed. Also it has been used to produce epoxy resins and polycarbonate plastics for food container. This study was carried out to investigate the effects of bisphenol A on lactation period to dams and F1. Sprague-Dawley females were mated with on 2 : 1 ratio basis. Various doses of bisphenol A (0, 2, 20, 200, and 2,000 ${\mu}g kg^{-1}$) were daily administered to females for 21 days after parturition. Dams and offsprings were sacrificed at the time of weaning. The results were as fellows, 2000 ${\mu}g \; kg^{-1}$ / of bisphenol A decreased the dams' body weight at post-partum 18 days and also 200 and 2,000 ${\mu}g \;kg^{-1}$ of bisphenol A decreased the body weight of neonates at the days of post-partum 21 days. Bisphenol A increased the relative weights of liver and spleen in male offsprings, depending on the doses. But female offsprings showed high relative organ weights of ovaries, and low relative organ weights of uterine in a some dose-response manners. High dose of bisphenol A induced low viability of neonates exposed during lactation period. The dams treated with bisphenol A showed prematured estrous stage. Bisphenol A was recovered about 21.2% average in serum of dams, and also in offsprings'. The results indicate that the bisphenol A induces estrous cycle during lactation period in dams, also reaches to the offspring through breast milk. Thus bisphenol A exopsed to dams and neonates via lactation induces some estrogenic and tonic effects.

• Molecular & Cellular Toxicology
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• v.5 no.3
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• pp.216-221
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• 2009

Bisphenol A (BPA) is commonly used in the production of pharmaceutical, industrial, and housing epoxy, as well as polycarbonate plastics. Owing to its extensive use, BPA can contaminate the environment either directly or through derivatives of these products. BPA has been classified as an endocrine disruptor chemicals (EDCs), and the primary toxicity of these EDCs in males involves the induction of reproductive system abnormality. First, in order to evaluate the direct effects on the Y chromosome associated with reproduction, we evaluated Y chromosome abnormalities using a Y chromosome microdeletion detection kit. However, we detected no Yq abnormality as the result of BPA exposure. Secondly, we performed high-density oligonucleotide array-based comparative genome hybridization (CGH) to assess genomic alteration as a component of our toxicity assessment. The results of our data analysis revealed some changes in copy number. Seven observed features were gains or losses in chromosomal DNA (P-value<1.0e-5, average log2 ratio>0.2). Interestingly, 21 probes of chr7:7312289-10272836 (qA1-qA2 in cytoband) were a commonly observed amplification (P-value 3.69e-10). Another region, chr14:4551029-10397399, was also commonly amplified (P-value 2.93e-12, average of log2 ratios in segment>0.3786). These regions include many genes associated with pheromone response, transcription, and signal transduction using ArrayToKegg software. These results help us to understand the molecular mechanisms underlying the reproductive effects induced by BPA.

• Toxicological Research
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• v.33 no.2
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• pp.165-171
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• 2017

Bisphenol A (BPA) is a monomer used in a polymerization reaction in the production of polycarbonate plastics. It has been used in many consumer products, including plastics, polyvinyl chloride, food packaging, dental sealants, and thermal receipts. However, there is little information available on the inhalation toxicity of BPA. Therefore, the aim of this study was to determine its inhalation toxicity and effects on the estrous cycle, spatial learning, and memory. Sprague-Dawley rats were exposed to 0, 10, 30, and $90mg/m^3$ BPA, 6 hr/day, 5 days/week for 8 weeks via whole-body inhalation. Mortality, clinical signs, body weight, hematology, serum chemistry, estrous cycle parameters, performance in the Morris water maze test, and organ weights, as well as gross and histopathological findings, were compared between the control and BPA exposure groups. Statistically significant changes were observed in serum chemistry and organ weights upon exposure to BPA. However, there was no BPA-related toxic effect on the body weight, food consumption, hematology, serum chemistry, organ weights, estrous cycle, performance in the Morris water maze test, or gross or histopathological lesions in any male or female rats in the BPA exposure groups. In conclusion, the results of this study suggested that the no observable adverse effect level (NOAEL) for BPA in rats is above $90mg/m^3$/6 hr/day, 5 days/week upon 8-week exposure. Furthermore, BPA did not affect the estrous cycle, spatial learning, or memory in rats.