Parabens inhibit the early phase of folliculogenesis and steroidogenesis in the ovaries of neonatal rats
Parabens inhibit the early phase of folliculogenesis and steroidogenesis in the ovaries of neonatal rats
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DOI：
10.1002/mrd.22070
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发表时间：
2012-09-01
影响因子：
2.5
通讯作者：
Jeung, Eui-Bae
中科院分区：
文献类型：
--
作者：
Ahn, Hyo-Jin;An, Beum-Soo;Jeung, Eui-Bae
对羟基苯甲酸酯广泛用作化妆品和制药工业中的抗微生物剂。最近，对羟基苯甲酸酯已被证明作为异种雌激素，一类内分泌干扰物。在本研究中，55只雌性幼仔在新生第17天每天皮下注射尼泊金甲酯、尼泊金丙酯和尼泊金丁酯或17 β-雌二醇（E2）。产后第8天切除卵巢，然后固定并用苏木素和伊红染色进行组织学分析。对卵泡进行计数，并将其分类为原始、早期初级或初级阶段。在高剂量的对羟基苯甲酸丙酯和对羟基苯甲酸丁酯下，原始卵泡的数量增加，而早期初级卵泡减少。抗苗勒管激素（AMH）和Foxl 2 mRNA的水平增加，而试剂盒配体/干细胞因子（KITL）的表达上调，只有对羟基苯甲酸丁酯。星星和Cyp 11 a1的mRNA水平显着下降后，与甲基，丙基，丁基对羟基苯甲酸酯处理。与其作为阳性对照的用途一致，E2调节KITL、星星和Cyp 11 a1基因的表达，但令人惊讶的是不影响AMH和Foxl 2水平。因此，E2和对羟基苯甲酸酯对卵泡生成和类固醇生成基因的调节有不同的影响，表明对羟基苯甲酸酯在卵巢中的雌激素和非雌激素性质。综上所述，我们的数据表明，对羟基苯甲酸酯刺激AMH mRNA的表达，从而抑制卵泡发育的早期阶段的新生雌性大鼠的卵巢。类固醇生成酶的水平，卵泡分化的指标，似乎是由对羟基苯甲酸酯通过抑制其转录抑制因子，Foxl 2的调节。摩尔Reprod. Dev. 79：626636，2012. (C)2012 Wiley Periodicals，Inc.
Parabens are widely used as anti-microbial agents in the cosmetic and pharmaceutical industries. Recently, parabens have been shown to act as xenoestrogens, a class of endocrine disruptors. In the present study, 55 female pups were given daily subcutaneous injections of methyl-, propyl-, and butyl-paraben or 17beta-estradiol (E2) during neonatal Day 17. The ovaries were excised on postnatal Day 8, then fixed and stained with hematoxylin and eosin for histological analysis. The follicles were counted and classified as being in the primordial, early primary, or primary stages. The number of primordial follicles increased while early primary follicles decreased at the high doses of propyl- and butyl-paraben. The levels of anti-Mullerian hormone (AMH) and Foxl2 mRNA increased by propyl- and butyl-parabens whereas kit ligand/stem cell factor (KITL) expression was up regulated only by butyl-paraben. The mRNA levels of StAR and Cyp11a1 were significantly decreased after treatment with methyl-, propyl-, and butyl-parabens. Consistent with its use as a positive control, E2 regulated the expression of KITL, StAR, and Cyp11a1 genes, but surprisingly did not affect AMH and Foxl2 levels. Thus, E2 and parabens had different effects on the regulation of folliculogenic and steroidogenic genes, demonstrating the estrogenic and nonestrogenic properties of parabens in the ovary. Taken together, our data show that parabens stimulated AMH mRNA expression and consequently inhibited the early phase of folliculogenesis in the ovaries of neonatal female rat. The levels of steroidogenic enzymes, indicators of follicle differentiation, appeared to be regulated by parabens through inhibition of their transcriptional repressor, Foxl2. Mol. Reprod. Dev. 79: 626636, 2012. (C) 2012 Wiley Periodicals, Inc.