Multiple Endocrine Disrupting Effects in Rats Perinatally Exposed to Butylparaben
Multiple Endocrine Disrupting Effects in Rats Perinatally Exposed to Butylparaben
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DOI：
10.1093/toxsci/kfw079
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发表时间：
2016-07-01
影响因子：
3.8
通讯作者：
Hass, U.
中科院分区：
文献类型：
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作者：
Boberg, J.;Axelstad, M.;Hass, U.
对羟基苯甲酸酯包括一组通常添加到化妆品、洗剂和其它消费品中的防腐剂。对羟基苯甲酸丁酯具有雌激素和抗雄激素特性，已知在围产期暴露后会减少大鼠的精子计数。然而，对羟基苯甲酸丁酯暴露是否会影响其他内分泌敏感终点，在很大程度上仍然未知。在本研究中，同期交配的Wistar大鼠（n = 18）从妊娠第7天至幼仔第22天经口暴露于0、10、100或500 mg/kg bw/d的对羟基苯甲酸丁酯。几个内分泌敏感性终点受到不利影响。在2个最高剂量组中，新生雄性和雌性后代的肛门生殖器距离显著缩短，在青春期前雌性中，卵巢重量降低，乳腺生长增加。在雄性后代中，精子数量在10 mg/kg bw/d以上的所有剂量下均显著减少。睾丸CYP 19 a1（芳香化酶）表达减少青春期前，但成年动物暴露于对羟基苯甲酸丁酯。在成年睾丸中，Nr 5a 1表达在所有剂量下均降低，表明类固醇生成持续中断。青春期前前列腺组织学改变，高剂量组成年前列腺重量降低。因此，对羟基苯甲酸丁酯对雄性和雌性后代都产生了内分泌干扰作用。在最低剂量下观察到的对精子计数的不良发育影响与风险评估高度相关，因为这是在围产期暴露于对羟基苯甲酸丁酯的研究中观察到的最低不良影响水平。
Parabens comprise a group of preservatives commonly added to cosmetics, lotions, and other consumer products. Butylparaben has estrogenic and antiandrogenic properties and is known to reduce sperm counts in rats following perinatal exposure. Whether butylparaben exposure can affect other endocrine sensitive endpoints, however, remains largely unknown. In this study, time-mated Wistar rats (n = 18) were orally exposed to 0, 10, 100, or 500 mg/kg bw/d of butylparaben from gestation day 7 to pup day 22. Several endocrine-sensitive endpoints were adversely affected. In the 2 highest dose groups, the anogenital distance of newborn male and female offspring was significantly reduced, and in prepubertal females, ovary weights were reduced and mammary gland outgrowth was increased. In male offspring, sperm count was significantly reduced at all doses from 10 mg/kg bw/d. Testicular CYP19a1 (aromatase) expression was reduced in prepubertal, but not adult animals exposed to butylparaben. In adult testes, Nr5a1 expression was reduced at all doses, indicating persistent disruption of steroidogenesis. Prostate histology was altered at prepuberty and adult prostate weights were reduced in the high dose group. Thus, butylparaben exerted endocrine disrupting effects on both male and female offspring. The observed adverse developmental effect on sperm count at the lowest dose is highly relevant to risk assessment, as this is the lowest observed adverse effect level in a study on perinatal exposure to butylparaben.