사춘기 전 수컷 흰쥐의 저정낭과 전립선의 성숙에 미치는 di(2-ethylhexyl) phthalate(DEHP)의 영향
Effect of Prepubertal Exposure to Di(2-ethylhexyl) phthalate on the Maturation of Rat Seminal Vesicles and Prostate Glands
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The plasticizer di(2-ethylhexyl) phthalate(DEHP) is one of the most well known endocrine disrupting chemicals(EDCs) because of its strong anti-androgenic effects on the reproductive and developmental process in male rodents and human. The present study was performed to examine whether prepubertal exposure to DEHP can make any alteration during the maturation of accessory sex organs in male rats. As a result, there was no significant change in body weights, serum T levels and tissue weights except of seminal vesicle and ventral prostate in DEHP-treated animals compared to vehicle-treated ones. The seminal vesicle weights in high-dose group(200mg/kg) were significantly lower than those from the control group(p<0.05), and ventral prostate weights were significantly lower than those from the control group(p<0.05) in both low-dose(20mg/kg) and high-dose group. Histological studies revealed that the seminal vesicles from DEHP-treated groups showed reduced areas of mucosal folds. Pseudostratified columnar epithelia were observed in the ventral prostates of DEHP-treated samples while cuboidal epithelia were found in the control group. The transcriptional activities of ER-α in seminal vesicle from high-dose group(p<0.05) were significantly higher than those from the control group, and ER-β expression was significantly decreased in low-dose group(p<0.05) compared to the control. In ventral prostate, ER-β mRNA levels from low-dose group(p<0.05) were significantly lower than those from the control group, and significantly increased in high-dose group(p<0.001). AR expressions, however, were not significantly different in all experimental groups of both seminal vesicle and ventral prostate. In conclusion, the present study demonstrated that (i) adverse effect(s) of DEHP on sexual maturation during prepubertal period could be limited, (ii) seminal vesicle and prostate gland were sensitive targets to DEHP in prepubertal rats and (iii) the deleterious effects of DEHP might be mediated through ER-associated mechanism
Abstract
The plasticizer di(2-ethylhexyl) phthalate(DEHP) is one of the most well known endocrine disrupting chemicals(EDCs) because of its strong anti-androgenic effects on the reproductive and developmental process in male rodents and human. The present study was performed to examine whether prepubertal exposure to DEHP can make any alteration during the maturation of accessory sex organs in male rats. As a result, there was no significant change in body weights, serum T levels and tissue weights except of seminal vesicle and ventral prostate in DEHP-treated animals compared to vehicle-treated ones. The seminal vesicle weights in high-dose group(200mg/kg) were significantly lower than those from the control group(p<0.05), and ventral prostate weights were significantly lower than those from the control group(p<0.05) in both low-dose(20mg/kg) and high-dose group. Histological studies revealed that the seminal vesicles from DEHP-treated groups showed reduced areas of mucosal folds. Pseudostratified columnar epithelia were observed in the ventral prostates of DEHP-treated samples while cuboidal epithelia were found in the control group. The transcriptional activities of ER-α in seminal vesicle from high-dose group(p<0.05) were significantly higher than those from the control group, and ER-β expression was significantly decreased in low-dose group(p<0.05) compared to the control. In ventral prostate, ER-β mRNA levels from low-dose group(p<0.05) were significantly lower than those from the control group, and significantly increased in high-dose group(p<0.001). AR expressions, however, were not significantly different in all experimental groups of both seminal vesicle and ventral prostate. In conclusion, the present study demonstrated that (i) adverse effect(s) of DEHP on sexual maturation during prepubertal period could be limited, (ii) seminal vesicle and prostate gland were sensitive targets to DEHP in prepubertal rats and (iii) the deleterious effects of DEHP might be mediated through ER-associated mechanism
참고문헌 (28)
- Agarwal DK, "Effects of di(2-ethylhexyl) phthalate on the gonadal pathophysiology, sperm morphology, and reproductive performance of male rats", Environ Health Perspect, 65, pp.343~350 (1986)
- Akingbemi BT, "Modulation of rat Leydig cell steroidogenic function by di (2-ethylhexyl)phthalate", Biol Reprod, 65, pp.1252~1259 (2001)
- Akingbemi BT, "Phthalate-induced Leydig cell hyperplasia is associated with multiple endocrine disturbances", Proc Natl Acad Sci USA, 101, pp.775~780 (2004)
- Andrade AJ, "A dose response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): reproductive effects on adult male offspring rats", Toxicology, 228, pp.85~97 (2006)
- Chomzynski P, "Single-step method of RNA isolation by RNA guanidium thiocyanate phenol- chloroform extraction", Anal Biochem, 162, pp.156~159 (1987)
- Dalsenter PR, "Phthalate affect the reproductive function and sexual behavior of male Wistar rats", Hum Exp Toxicol, 25, pp.297~303 (2006)
- Foster PM, "Effects of phthalate esters on the developing reproductive tract of male rats", Hum Reprod Update, 7, pp.231~235 (2001)
- Gangolli SD, "Testicular effects of phthalate esters", Environ Health Perspect, 45, pp.77~84 (1982)
- Ge RS, "Biphasic effects of postnatal exposure to diethylhexylphthalate on the timing of puberty in male rats", J Androl, 28, pp.513~520 (2007)
- Gray LE Jr, "Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat", Toxicol Sci, 58, pp.350~365 (2000)
- Hotchkiss AK, "Fifteen years after “Wingspread”- environmental endocrine disrupters and human and wildlife health: where we are today and where we need to go", Toxicol Sci, 105, pp.235~259 (2008)
- Hoyer PB, "Reproductive toxicology: current and future directions", Biochem Pharmacol, 62, pp.1557~1564 (2001)
- Jarfelt K, "Antiandrogenic effects in male rats perinatally exposed to a mixture of di(2-ethylhexyl) phthalate and di(2-ethylhexyl) adipate", Reprod Toxicol, 19, pp.505~515 (2005)
- Kim SK, "Octylphenol reduces the expressions of steroidogenic enzymes and testosterone production in mouse testis", Environ Toxicol, 22, pp.449~458 (2007)
- Koch HM, "An estimation of the daily intake of di(2-ethylhexyl)phthalate (DEHP) and other phthalates in the general population", Int J Hyg Environ Health, 206, pp.77~83 (2003)
- Koch HM, "Di(2-ethylhexyl) phthalate (DEHP): human metabolism and internal exposure- an update and latest results", Int J Androl, 29, pp.155~165 (2006)
- Kurahashi N, "The effects of subacute inhalation of di (2-ethylhexyl) phthalate (DEHP) on the testes of prepubertal Wistar rats", J Occup Health, 47, pp.437~444 (2005)
- Latini G, "Monitoring phthalate exposure in humans", Clin Chim Acta, 361, pp.20~29 (2005)
- Latini G, "Phthalate exposure and male infertility", Toxicology, 226, pp.90~98 (2006)
- 이경엽, "암컷 흰쥐의 사춘기 개시에 미치는 di(2-ethyl gexyl)phthalate(DEHP)의 효과", 발생과 생식, 10(2), pp.147~154 (2006), 한국발생생물학회
- 이경엽, "내분비계 장애물질이 미성숙한 흰쥐의 난소와 자궁에서의 에스트로겐 수용체 발현에 미치는 효과", 발생과 생식, 10(4), pp.255~261 (2006), 한국발생생물학회
- Ma M, "Exposure of prepubertal female rats to inhaled di(2-ethylhexyl)phthalate affects the onset of puberty and postpubertal reproductive functions", Toxicol Sci, 93, pp.164~171 (2006)
- Mäkelä S, "Differential expression of estrogen receptors alpha and beta in adult rat accessory sex glands and lower urinary tract", Mol Cell Endocrinol, 170, pp.219~229 (2000)
- Moore RW, "Abnormalities of sexual development in male rats with in utero and lactational exposure to the antiandrogenic plasticizer Di(2-ethylhexyl) phthalate", Environ Health Perspect, 109, pp.229~237 (2001)
- Ryu JY, "Di(2-ethylhexyl) phthalate induces apoptosis through peroxisome proliferators-activated receptor-gamma and ERK 1", 2 activation in testis of Sprague-Dawley rats, 2007, pp.70, 1296~1303
- Schoeters G, "Endocrine disruptors and abnormalities of pubertal development", Basic Clin Pharmacol Toxicol, 102, pp.168~175 (2008)
- Teilmann G, "Putative effects of endocrine disrupters on pubertal development in the human", Best Pract Res Clin Endocrinol Metab, 16, pp.105~121 (2002)
- Wittassek M, "Daily intake of di(2-ethylhexyl) phthalate (DEHP) by German children - A comparison of two estimation models based on urinary DEHP metabolite levels", Int J Hyg Environ Health, 210, pp.35~42 (2007)