Di-(2-ethylhexyl) phthalate and mono-(2-ethylhexyl) phthalate inhibit growth and reduce estradiol levels of antral follicles in vitro.
Di-(2-ethylhexyl) phthalate and mono-(2-ethylhexyl) phthalate inhibit growth and reduce estradiol levels of antral follicles in vitro.
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DOI：
10.1016/j.taap.2009.10.011
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发表时间：
2010-01-15
影响因子：
3.8
通讯作者：
Yao HH
中科院分区：
文献类型：
--
作者：
Gupta RK;Singh JM;Leslie TC;Meachum S;Flaws JA;Yao HH
任何影响卵巢有腔卵泡存活的侮辱都可能导致雌二醇的异常产生和生育问题。邻苯二甲酸酯(PE)是广泛用于消费品和工业产品的增塑剂。接触这些化学物质与人类和动物模型的生育力下降有关。邻苯二甲酸二(2-乙基己基)酯(DEHP)和邻苯二甲酸单(2-乙基己基)酯(MEHP)可降低动物和培养模型的血清雌二醇水平和芳香化酶(AROM)的表达，延长发情周期，并导致无排卵。这些观察结果表明，PES直接针对有腔卵泡。因此，我们验证了DEHP(1-100微克/毫升)和MEHP(0.1-10微克/毫升)直接抑制有腔卵泡生长和雌二醇产生的假设。成年小鼠的有腔卵泡用DEHP或MEHP和/或雌二醇培养96h。在培养过程中，每隔24小时测量一次卵泡大小，以此来衡量卵泡的生长。培养结束后，收集培养上清液测定雌二醇水平，并测定卵泡细胞周期蛋白D-2(CCND2)、细胞周期蛋白依赖性激酶-4(CDK4)和AROM的表达。我们发现，与对照组相比，DEHP和MEHP在最高剂量下抑制了卵泡的生长，并减少了雌二醇的产生。DEHP和MEHP还能降低CCND2、CDK4和AROM的mRNA表达。在培养液中加入雌二醇可阻止DEHP和MEHP对卵泡生长的抑制，降低雌二醇水平，并减少CCND2和CDK4的表达。综上所述，我们的结果表明DEHP和MEHP可能直接抑制有腔卵泡的生长，其机制部分包括减少雌二醇的产生和减少细胞周期调节因子的表达。
Any insult that affects survival of ovarian antral follicles can cause abnormal estradiol production and fertility problems. Phthalate esters (PEs) are plasticizers used in wide range of consumer and industrial products. Exposure to these chemicals has been linked to reduced fertility in humans and animal models. Di-(2-ethylhexyl) phthalate (DEHP) and Mono-(2-ethylhexyl) phthalate (MEHP) decreases serum estradiol levels and aromatase (Arom) expression, prolongs estrous cycles, and causes anovulation in animal and culture models. These observations suggest PEs directly target antral follicles. We therefore tested the hypothesis that DEHP (1–100 µg/ml) and MEHP (0.1–10 µg/ml) directly inhibit antral follicular growth and estradiol production. Antral follicles from adult mice were cultured with DEHP or MEHP, and/or estradiol for 96 hrs. During culture, follicle size was measured every 24 hrs as a measurement of follicle growth. After culture, media was collected for measurement of estradiol levels and follicles were subjected to measurement of cylin-D-2 (Ccnd2), cyclin-dependant-kinase-4 (Cdk4), and Arom. We found that DEHP and MEHP inhibited growth of follicles and decreased estradiol production compared to controls at highest doses. DEHP and MEHP also decreased mRNA expression of Ccnd2, Cdk4, and Arom with highest dose. Addition of estradiol to the culture medium prevented the follicles from DEHP- and MEHP-induced inhibition of growth, reduction in estradiol levels, and decreased Ccnd2 and Cdk4 expression. Collectively, our results indicate that DEHP and MEHP may directly inhibit antral follicle growth via a mechanism that partially includes reduction in levels of estradiol production and decreased expression of cell cycle regulators.
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影响因子：
13.3
作者：
Cortvrindt, RG;Smitz, JEJ
通讯作者：
Smitz, JEJ
影响因子：
3.8
作者：
Miller, KP;Gupta, RK;Flaws, JA
通讯作者：
Flaws, JA
影响因子：
3.5
作者：
Lenie, Sandy;Smitz, Johan
通讯作者：
Smitz, Johan
DOI：
10.1078/1438-4639-00309
发表时间：
2004-10-01
影响因子：
6
作者：
Becker, K;Seiwert, M;Ullrich, D
通讯作者：
Ullrich, D
影响因子：
--
作者：
Kumar, Premlata;Kamat, Amrita;Mendelson, Carole R.
通讯作者：
Mendelson, Carole R.