Steroidogenesis in fetal male rats is reduced by DEHP and DINP, but endocrine effects of DEHP are not modulated by DEHA in fetal, prepubertal and adult male rats
Steroidogenesis in fetal male rats is reduced by DEHP and DINP, but endocrine effects of DEHP are not modulated by DEHA in fetal, prepubertal and adult male rats
复制标题
DOI：
10.1016/j.reprotox.2003.10.011
复制
发表时间：
2004-01-01
影响因子：
3.3
通讯作者：
Vinggaard, AM
中科院分区：
文献类型：
--
作者：
Borch, J;Ladefoged, O;Vinggaard, AM
增塑剂邻苯二甲酸二(2-乙基己基)酯(DEHP)在围产期暴露的雄性大鼠中显示出抗雄激素的作用。己二酸二(2-乙基己基)酯(DEHA)和邻苯二甲酸二异农酯(DINP)目前被认为是DEHP的潜在替代品，但DEHP与DEHA和DINP在结构和代谢上的相似性导致了这样的假设：也可能存在相似的作用。妊娠及哺乳期Wistar大鼠分别用DEHP(300或750 mg/kg体重/d)、DINP(750 mg/kg体重/d)、DEHP(750 mg/kg体重/d)联合DEHA(400 mg/kg体重/d)或DEHP(300 mg/kg体重/d)+DINP(750 mg/kg体重/d)灌胃。DINP和DEHP均能降低体外培养的雄性胎儿睾丸睾酮的生成，降低妊娠21天男性胎儿睾丸和血浆中的睾酮水平，表明DINP和DEHP的作用机制相似。此外，男性胎儿的血浆黄体生成素水平也升高。暴露于DEHP的雄性子代出生后第13天，新生儿肛门距离缩短，乳头数量增加。在暴露于DEHP的青春期前雄性后代中，血清抑制素B水平显著降低，在少数成年雄性中也是如此。DEHA对DEHP的内分泌作用无调节作用，但DEHP与DINP合用有抑制睾酮合成的蓄积作用。(C)2003 Elsevier Inc.保留所有权利。
The plasticizer di(2-ethylhexyl)phthalate (DEHP) exhibits antiandrogenic effects in perinatally exposed male rats. Di(2-ethylhexyl) adipate (DEHA) and diisononyl phthalate (DINP) are currently being evaluated as potential substitutes for DEHP, but similarities in structure and metabolism of DEHP with DEHA and DINP have led to the hypothesis that similarities inaction may also exist. Pregnant Wistar rats were gavaged during gestation and lactation with vehicle, DEHP (300 or 750 mg/kg bodyweight per day), DINP (750 mg/kg bodyweight per day), DEHP (750 mg/kg bodyweight per day) in combination with DEHA (400 mg/kg bodyweight per day), or DEHP (300 mg/kg bodyweight per day) in combination with DINP (750 mg/kg bodyweight per day). DINP and DEHP were both shown to reduce testicular testosterone production ex vivo and testosterone levels in testes and plasma of male fetuses at gestation day 2 1, indicating a similar mechanism of action for DINP and DEHP. Additionally, plasma LH levels in male fetuses were elevated. Neonatal anogenital distance was reduced and the number of nipples at postnatal day 13 increased in DEHP-exposed male offspring. Serum inhibin B levels were significantly reduced in DEHP-exposed prepubertal male offspring, and in a few adult males. No modulating effects of DEHA on the endocrine effects of DEHP were detected, but a tendency towards an accumulating effect of DEHP and DINP in combination on suppression of testosterone synthesis was seen. (C) 2003 Elsevier Inc. All rights reserved.