Role of the 17β-hydroxysteroid dehydrogenase signalling pathway in di-(2-ethylhexyl) phthalate-induced ovarian dysfunction: An in vivo study
Role of the 17β-hydroxysteroid dehydrogenase signalling pathway in di-(2-ethylhexyl) phthalate-induced ovarian dysfunction: An in vivo study
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17β-羟基类固醇脱氢酶信号通路在邻苯二甲酸二(2-乙基己基)酯诱导的卵巢功能障碍中的作用：一项体内研究
DOI：
10.1016/j.scitotenv.2019.134406
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发表时间：
2020-04-10
影响因子：
9.8
通讯作者：
Ye, Lin
中科院分区：
文献类型：
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作者：
Li, Na;Zhou, Liting;Ye, Lin
增塑剂邻苯二甲酸二（2-乙基己基）酯（DEHP）与女性生殖内分泌毒性有关。我们之前的研究发现，DEHP的代谢产物邻苯二甲酸单（2-乙基己基）酯（MEHP）可通过体外17 β-羟基类固醇脱氢酶（17 β-HSD）失调干扰卵巢功能。本研究的目的是在体内验证这一假设。本研究验证了亚急性暴露于DEHP通过失调17 β-HSD信号传导诱导卵巢功能障碍的假设。将48只成年雌性Wistar大鼠随机分为4组：对照组、低剂量组、中剂量组和高剂量组。DEHP以0、300、1000和3000 mg/kg/d（体重）的剂量灌胃4周。处死大鼠，检测卵巢病理变化、性激素水平、性激素合成途径中类固醇受体表达、类固醇生成酶表达及GC凋亡情况。本研究表明，DEHP可延长动情周期，增加卵泡闭锁，抑制性激素分泌，减少类固醇生成酶的表达，促进GCs凋亡，与卵巢功能障碍有关。总之，这些结果表明DEHP可通过17 β-HSD信号通路干扰卵巢功能。(C)2019 Elsevier B. V.版权所有。
Plasticiser di-(2-ethylhexyl) phthalate (DEHP) is associated with female reproductive endocrine toxicity. Our previous study found that mono-(2-ethylhexyl) phthalate (MEHP), the metabolite of DEHP, can interfere with ovarian function via dysregulation of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) in vitro. The aim of this study was to verify this hypothesis in vivo. The present study tested the hypothesis that subacute exposure to DEHP induced ovarian dysfunction by dysregulating 17 beta-HSD signalling. 48 adult female Wistar rats were divided into 4 groups randomly: control group, low-dose group, medium-dose group, and high-dose group. DEHP was intragastrically administrated at the dosage of 0, 300, 1000 and 3000 mg/kg/d (body weight) for 4 weeks. Rats were executed, and the detection of the pathological changes of ovaries, steroid hormone levels, steroid receptor expression, and steroidogenic enzyme expression in sex hormone synthesis pathway and the apoptosis of GCs were performed. This study showed that DEHP could prolong the estrous cycle, increase follicular atresia, inhibit sex hormone secretion, reduce the expression of steroidogenic enzymes, and promote GCs apoptosis associating with ovarian dysfunction. In conclusion, these results indicate that DEHP can disturb ovarian function through the 17 beta-HSD signalling pathway. (C) 2019 Elsevier B.V. All rights reserved.