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Effects of Phthalate/Adipate Esters Exposure during Perinatal Period on Reproductive Function after Maturation in Rats

성숙한 랫트의 번식 기능에 있어 프탈레이트/아디페이트 에스테르의 주산기 노출의 영향

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  • Yamanouchi, K. (Department of Veterinary Physiology, Tokyo University) ;
  • Nishihara, M. (Department of Veterinary Physiology, Tokyo University)
  • Published : 2006.10.31

Abstract

Phthalate esters that are used as plasticizers and also found at low levels in foods such as dairy products are often mentioned as suspected endocrine disrupters. The purpose of the present study is to elucidate whether perinatal exposure to di-n-butyl phthalate(DBP), diisononyl phthalate (DINP) and di-2-ethylhexyl adipate (DEHA) affects several aspects of reproductive function in rats especially sexual differentiation of the brain. To this end, the dams were provided with pulverized soy-free diet containing 20, 200, 2,000 and 10,000 ppm of DBP, 40, 400, 4,000 and 20,000 ppm of DINP, or 480, 2,400 and 12,000 ppm of DEHA from gestational day (GD) 15 to postnatal day (PDN) 21, the day of weaning, and serum sex steroid hormone, gonadotropin levels and sexual behaviors after maturation were assessed. At Postnatal week (PNW) 20-21, serum levels of sex steroids and gonadotropins in both male and female rats, as well as estrous cyclicity in females, were not changed by perinatal exposure to DBP, DINP and DEHA, indicating that these chemicals did not affect sexual differentiation of the brain controlling the endocrine system of hypothalamo-pituitary-gonadal (HPG) axis. On the other hand, inhibitory influences on sexual behaviors, especially on ejaculation in males and lordosis in females, were observed by perinatal exposure to these chemicals. These results suggest that these chemicals may act directly on discrete regions of the hypothalamus regulating sexual behaviors, but not regulating gonadotropin secretion, thereby affect sexual differentiation of the brain with a resultant decrease in sex-specific behaviors in adulthood.

프탈레이트 에스테르는 플라스틱 가소제로서 이용되며 또한 유제품과 같은 음식에서 미량으로 발견되고, 종종 내분비 교란물질로 의심되고 있다. 본 연구의 목적은 DBP, DINP 또는 DEHA의 주산기 노출이 랫트에 있어 성 성숙 후, 번식기능 특히 뇌의 성분화에 어떤 영향을 끼치는 지에 대해 조사하였다. 이를 수행하기 위해서, 어미에게 식물성 에스트로겐의 함유가 낮은 분말 사료에 다음과 같은 단계적 농도의 DBP (20, 200, 2000, 10000 ppm), DINP (40, 400, 4000, 20000 ppm), DEHA (480, 2400, 12000 ppm)를 혼합한 후, 임신 15일째부터 출생 후, 21일째 (이유기)까지 섭취 시켰고, 성 성숙 후, 혈청 성호르몬 및 성선자극호르몬의 레벨과 교배행동 및 성주기 회귀를 분석하였다. 그 결과, DBP, DINP 또는 DEHA의 주산기 노출에 의한 생후 20~21주째의 암수 랫트에 있어, 성호르몬 및 성선자극호르몬의 레벨뿐만 아니라 암컷의 성주기의 회귀에 대해 어떠한 영향을 주지 않았다. 이것은 시상하부-하수체-성선축의 내분비계를 제어하는 뇌의 성분화에는 이들 화학물질이 영향을 주지 않았다는 사실을 시사한다. 하지만, 수컷의 성행동 특히, 사정 (ejaculation)과 암컷의 로도시스 반응이 억제되는 것이 관찰되었다. 이러한 결과로부터 DBP, DINP 또는 DEHA의 주산기 노출은 성선자극 호르몬의 분비에는 영향을 주지 않지만, 성행동을 제어하는 시상하부의 어떤 영역에 직접적으로 작용할 가능성 즉, 뇌의 성분화에 영향을 끼쳐 성 성숙 후, 성 특이적 행동을 억제시킬 가능성을 시사한다.

Keywords

References

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