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Study of fibroblast growth factor 2 administration in bleomycin induced pulmonary fibrosis mice
Se Bi Lee,Hyeokku Lee,Jungyu Baek,Eunhyeok Choi,Hyunseung Lee,Juhyeok Hong,Jaehyun Kim,Jeong Yun Park,Gichang Jeong,Jieun Jeon,Jooyeon Lee,Jaehyun Park,Jimin Jang,Sang-Ryul Cha,Se-Ran Yang 한국실험동물학회 2023 한국실험동물학회 학술발표대회 논문집 Vol.2023 No.2
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Cha, Sunyeong,Jung, Kayeon,Lee, Min Young,Hwang, Yeon Jeong,Yang, Eunhyeok,Lee, Sung-Ho,Jung, Hyo-il,Cheon, Yong-Pil The Korean Society of Developmental Biology 2018 발생과 생식 Vol.22 No.1
Endocrine disruptors have been concerned in toxicology but now challenged as physiological point especially concerned with exposing dose and period. In this study the low-dose chronic administration of di(2-ethylhexyl) phthaltae (DEHP) during reproductive period was examined to evaluate the possible roles. Adult male and female CD-1 mice were exposed to DEHP with drinking water containing $133{\mu}g/L$ and $1,330{\mu}g/L$ DEHP in water according to OECD 433 guide line and sacrificed just after weaning. The weights of uterus and ovary were decreased by drinking of $1,330{\mu}g/L$ DEHP water. There was not adverse effects on either accumulated mating rate and mating rate depend on estrus stage, pregnancy duration, and sex ration at birth. However, the accumulated rate of successful delivery and litter size were significantly high at $1,330{\mu}g/L$ DEHP water. The number of epididymal sperm was significantly increased by drinking of $1,330{\mu}g/L$ DEHP water. In addition, the number of follicles (primary, secondary, tertiary) were more many than control at $1,330{\mu}g/L$ DEHP water drunk mother. Though further studies are needed to identify what are the mechanism of DEHP in folliculogenesis and spermatogenesis. From this study we firstly report the effect of low-dose chronic administration of DEHP with drinking could change the ovarian follicle population size and spermatogenesis rate. Put together, those finding is different from previous high-dose effects and suggest the physiological role of DEHP in gonads and uterus.
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Kim, Juhye,Cha, Sunyeong,Lee, Min Young,Hwang, Yeon Jeong,Yang, Eunhyeok,Ryou, Chongsuk,Jung, Hyo-Il,Cheon, Yong-Pil The Korean Society of Developmental Biology 2018 발생과 생식 Vol.22 No.4
Through the development of organic synthetic skill, chemicals that mimic signaling mediators such as steroid hormones have been exposed to the environment. Recently, it has become apparent that this circumstance should be further studied in the field of physiology. Estrogenic action of chronic low-dose nonylphenol (NP) and di-(2-ethylhexyl) phthalate (DEHP) in mouse uterus was assessed in this study. Ten to twelve-week-old female mice (CD-1) were fed drinking water containing NP (50 or $500{\mu}g/L$) or DEHP (133 or $1,330{\mu}g/L$) for 10 weeks. Uterine diameter, the thickness of myometrium and endometrium, and the height of luminal epithelial cells were measured and the number of glands were counted. The expression levels of the known $17{\beta}$-estradiol ($E_2$)-regulated genes were evaluated with real-time RT-PCR methodology. The ration of uterine weight to body weight increased in $133{\mu}g/L$ DEHP. Endometrial and myometrial thickness increased in 133 and $1,330{\mu}g/L$ DEHP treated groups, and in 50, $500{\mu}g/L$ NP and $133{\mu}g/L$ DEHP, respectively. The height of luminal epithelial cell decreased in NP groups. The numbers of luminal epithelial gland were decreased in NP groups but increased in $50{\mu}g/L$ DEHP group. The histological characters of glands were not different between groups. The mRNA expression profiles of the known $17{\beta}$-estradiol ($E_2$) downstream genes, Esr1, Esr2, Pgr, Lox, and Muc1, were also different between NP and DEHP groups. The expression levels dramatically increased in some genes by the NP or DEHP. Based on these results, it is suggested that the chronic low-dose NP or DEHP works as estrogen-like messengers in uterus with their own specific gene expression-regulation patterns.
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Juhye Kim,Sunyeong Cha,Min Young Lee,Yeon Jeong Hwang,Eunhyeok Yang,Chongsuk Ryou,Hyo-Il Jung,전용필 한국발생생물학회 2018 발생과 생식 Vol.22 No.4
Through the development of organic synthetic skill, chemicals that mimic signaling mediators such as steroid hormones have been exposed to the environment. Recently, it has become apparent that this circumstance should be further studied in the field of physiology. Estrogenic action of chronic low-dose nonylphenol (NP) and di-(2-ethylhexyl) phthalate (DEHP) in mouse uterus was assessed in this study. Ten to twelve-week-old female mice (CD-1) were fed drinking water con-taining NP (50 or 500 μg/L) or DEHP (133 or 1,330 μg/L) for 10 weeks. Uterine diameter, the thickness of myometrium and endometrium, and the height of luminal epithelial cells were measured and the number of glands were counted. The expres-sion levels of the known 17-estradiol (E2)-regulated genes were evaluated with real-time RT-PCR methodology. The ration of uterine weight to body weight increased in 133 g/L DEHP. Endometrial and myometrial thickness increased in 133 and 1,330 g/L DEHP treated groups, and in 50, 500 g/L NP and 133 g/L DEHP, respectively. The height of luminal epithelial cell decreased in NP groups. The numbers of gland were decreased in NP groups but increased in 50 g/L DEHP group. The histological characters of glands were not much different between groups. The mRNA expression profiles of the known 17β-estradiol (E2) downstream genes were also different between NP and DEHP groups. The expression levels dramatically in-creased in some genes by the NP or DEHP. Based on these results, it is suggested that the chronic low-dose NP or DEHP works as estrogen-like messengers in uterus with their own specific gene expression-regulation patterns.
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Sunyeong Cha,Kayeon Jung,Min Young Lee,Yeon Jeong Hwang,Eunhyeok Yang,Sung-Ho Lee,Hyo-il Jung,Yong-Pil Cheon 한국발생생물학회 2018 발생과 생식 Vol.22 No.1
Endocrine disruptors have been concerned in toxicology but now challenged as physiological point especially concerned with exposing dose and period. In this study the low-dose chronic administration of di(2-ethylhexyl) phthaltae (DEHP) during reproductive period was examined to evaluate the possible roles. Adult male and female CD-1 mice were exposed to DEHP with drinking water containing 133 g/L and 1,330 ㎍/L DEHP in water according to OECD 433 guide line and sacrificed just after weaning. The weights of uterus and ovary were decreased by drinking of 1,330 ㎍/L DEHP water. There was not adverse effects on either accumulated mating rate and mating rate depend on estrus stage, pregnancy duration, and sex ration at birth. However, the accumulated rate of successful delivery and litter size were significantly high at 1,330 ㎍/L DEHP water. The number of epididymal sperm was significantly increased by drinking of 1,330 ㎍/L DEHP water. In addition, the number of follicles (primary, secondary, tertiary) were more many than control at 1,330 ㎍/L DEHP water drunk mother. Though further studies are needed to identify what are the mechanism of DEHP in folliculogenesis and spermatogenesis. From this study we firstly report the effect of low-dose chronic administration of DEHP with drinking could change the ovarian follicle population size and spermatogenesis rate. Put together, those finding is different from previous high-dose effects and suggest the physiological role of DEHP in gonads and uterus.
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Kim, Juhye,Cha, Sunyeong,Lee, Min Young,Hwang, Yeon Jeong,Yang, Eunhyeok,Choi, Donchan,Lee, Sung-Ho,Cheon, Yong-Pil The Korean Society of Developmental Biology 2019 발생과 생식 Vol.23 No.3
Based on our preliminary results, we examined the possible role of low-dose and chronic-exposing of the chemicals those are known as endocrine disrupting chemical (EDC), on the proliferation of uterine endometrium and the localization of steroid receptors. Immunohistochemical or immunofluorochemical methodology were employed to evaluate the localization of antigen identified by monoclonal antibody Ki 67 protein (MKI67), estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), and progesterone receptor (PGR). In $133{\mu}g/L$ and $1,330{\mu}g/L$ di(2-ethylhexyl) phthalate (DEHP) and $50{\mu}g/L$ nonylphenol (NP) groups, the ratio of MKI67 positive stromal cells was significantly increased but not in $500{\mu}g/L$ NP group. The ratios of MKI67 positive glandular and luminal epithelial cells were also changed by the chronic administration of NP and DEHP in tissue with dose specific manner. ESR1 signals were localized in nucleus in glandular and luminal epithelia of control group but its localization was mainly in cytoplasm in DEHP and NP administered groups. On the other hand, it was decreased at nucleus of stromal cells in $1,330{\mu}g/L$ DEHP group. The colocalization patterns of these nuclear receptors were also modified by the administration of these chemicals. Such a tissue specific and dose specific localization of ESR2 and PGR were detected as ESR1 in all the uterine endometrial tissues. These results show that the chronic lows-dose exposing of NP or DEHP modify the localization and colocalization of ESRs and PGR, and of the proliferation patterns of the endometrial tissues.
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Sunyeong Cha,Jeong Won Baek,Hye Jin Ji,Jun Hee Choi,Chaelim Kim,Min Young Lee,Yeon Jeong Hwang,Eunhyeok Yang,Sung-Ho Lee,Hyo-il Jung,Yong-Pil Cheon 한국발생생물학회 2017 발생과 생식 Vol.21 No.2
4-Nonylphenol (NP) is a surfactant that is a well-known and widespread estrogenic endocrine disrupting chemical (EDC). Although it has been known that the affinity of NP to ERs is low, it has been suggested that low-dose NP has toxicity. In the present study, the endocrine disrupting effects on reproduction, and the weight of gonads, epididymis, and uterus were evaluated with the chronic lower-dose NP exposing. This study was designed by following the OECD test guideline 443 and subjected to a complete necropsy. In male, NP had an effect on the weight of the testis and epididymis in both F0 and F1. In females, NP decreased the weight of ovary and uterus in F0 but not in pre-pubertal F1 pubs. Fertility of male and female in F0 or F1 was no related with NP administration. The number of caudal-epididymal sperm by body weight (BW) was not different between groups in both F0 and F1. Besides, the difference of the sperm number between generations was not detected. The number of ovulated oocytes was similar between groups in F0, but significantly decreased in NP 50 group of F1. The litter size and sex ratios of offspring in F1 and F2 were not different. The accumulated mating rate and gestation period were not affected by the NP administration. Those results shows that chronic lower-dose NP administration has an effect of endocrine disruptor on the weight of gonads and epididymis of F0 and F1 but not in reproduction. Based on the results, it is suggested that chronic lower-dose NP exposing causes endocrine disruption in the weight of gonad and epididymis but not in the reproductive ability of next generations.
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Cha, Sunyeong,Baek, Jeong Won,Ji, Hye Jin,Choi, Jun Hee,Kim, Chaelim,Lee, Min Young,Hwang, Yeon Jeong,Yang, Eunhyeok,Lee, Sung-Ho,Jung, Hyo-il,Cheon, Yong-Pil The Korean Society of Developmental Biology 2017 발생과 생식 Vol.21 No.2
4-Nonylphenol (NP) is a surfactant that is a well-known and widespread estrogenic endocrine disrupting chemical (EDC). Although it has been known that the affinity of NP to ERs is low, it has been suggested that low-dose NP has toxicity. In the present study, the endocrine disrupting effects on reproduction, and the weight of gonads, epididymis, and uterus were evaluated with the chronic lower-dose NP exposing. This study was designed by following the OECD test guideline 443 and subjected to a complete necropsy. In male, NP had an effect on the weight of the testis and epididymis in both $F_0$ and $F_1$. In females, NP decreased the weight of ovary and uterus in $F_0$ but not in pre-pubertal $F_1$ pubs. Fertility of male and female in $F_0$ or $F_1$ was no related with NP administration. The number of caudal-epididymal sperm by body weight (BW) was not different between groups in both $F_0$ and $F_1$. Besides, the difference of the sperm number between generations was not detected. The number of ovulated oocytes was similar between groups in $F_0$, but significantly decreased in NP 50 group of $F_1$. The litter size and sex ratios of offspring in $F_1$ and $F_2$ were not different. The accumulated mating rate and gestation period were not affected by the NP administration. Those results shows that chronic lower-dose NP administration has an effect of endocrine disruptor on the weight of gonads and epididymis of $F_0$ and $F_1$ but not in reproduction. Based on the results, it is suggested that chronic lower-dose NP exposing causes endocrine disruption in the weight of gonad and epididymis but not in the reproductive ability of next generations.
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