Lee Jae-Hwan, Lee Myeongho, Ahn Changhwan, Kang Hee Young, Tran Dinh Nam, Jeung Eui-Bae
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Korea.
Int J Environ Res Public Health. 2017 Feb 8;14(2):161. doi: 10.3390/ijerph14020161.
Parabens are widely used preservatives in basic necessities such as cosmetic and pharmaceutical products. In previous studies, xenoestrogenic actions of parabens were reported in an immature rat model and a rat pituitary cell line (GH3 cells). The relationship between parabens and ovarian failure has not been described. In the present study, the influence of parabens on ovarian folliculogenesis and steroidogenesis was investigated. A disruptor of ovarian small pre-antral follicles, 4-vinylcyclohexene diepoxide (VCD, 40 mg/kg), was used to induce premature ovarian failure (POF). Methylparaben (MP, 100 mg/kg), propylparaben (PP, 100 mg/kg), and butylparaben (BP, 100 mg/kg) dissolved in corn oil were treated in female 8-week-old Sprague-Dawley rat for 5 weeks. Estrus cycle status was checked daily by vaginal smear test. Ovarian follicle development and steroid synthesis were investigated through real-time PCR and histological analyses. Diestrus phases in the VCD, PP, and BP groups were longer than that in the vehicle group. VCD significantly decreased mRNA level of folliculogenesis-related genes (, and ). All parabens significantly increased the mRNA level but unchanged and acting in primordial follicles. VCD and MP slightly increased and levels, which are related to an initial step in steroidogenesis. VCD and parabens induced an increase in FSH levels in serum and significantly decreased the total number of follicles. Increased FSH implies impairment in ovarian function due to VCD or parabens. These results suggest that VCD may suppress both formation and development of follicles. In particular, combined administration of VCD and parabens accelerated inhibition of the follicle-developmental process through elevated AMH level in small antral follicles.
对羟基苯甲酸酯是化妆品和药品等生活必需品中广泛使用的防腐剂。在以往的研究中，已报道对羟基苯甲酸酯在未成熟大鼠模型和大鼠垂体细胞系（GH3细胞）中具有外源性雌激素作用。对羟基苯甲酸酯与卵巢功能衰竭之间的关系尚未见描述。在本研究中，研究了对羟基苯甲酸酯对卵巢卵泡发生和类固醇生成的影响。使用卵巢小窦前卵泡破坏剂4-乙烯基环己烯二环氧化物（VCD，40mg/kg）诱导过早卵巢功能衰竭（POF）。将溶解于玉米油中的甲基对羟基苯甲酸酯（MP，100mg/kg）、丙基对羟基苯甲酸酯（PP，100mg/kg）和丁基对羟基苯甲酸酯（BP，100mg/kg）给予8周龄雌性Sprague-Dawley大鼠，处理5周。通过阴道涂片试验每日检查发情周期状态。通过实时PCR和组织学分析研究卵巢卵泡发育和类固醇合成。VCD组、PP组和BP组的动情间期长于溶剂对照组。VCD显著降低卵泡发生相关基因（、和）的mRNA水平。所有对羟基苯甲酸酯均显著增加mRNA水平，但对原始卵泡中的和无影响。VCD和MP轻微增加与类固醇生成第一步相关的和水平。VCD和对羟基苯甲酸酯诱导血清中FSH水平升高，并显著减少卵泡总数。FSH升高意味着VCD或对羟基苯甲酸酯导致卵巢功能受损。这些结果表明，VCD可能抑制卵泡的形成和发育。特别是，VCD和对羟基苯甲酸酯联合给药通过升高小窦状卵泡中的AMH水平加速了对卵泡发育过程的抑制。
