Propylparaben concentrations in the urine of women and adverse effects on ovarian function in mice in vivo and ovarian cells in vitro
Propylparaben concentrations in the urine of women and adverse effects on ovarian function in mice in vivo and ovarian cells in vitro
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DOI：
10.1002/jat.4225
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发表时间：
2021-08
影响因子：
3.3
通讯作者：
Luwei Jiao;Shang Li;Junyu Zhai;Dongshuang Wang;Hongwanyu Li;Weiwei Chu;Xueying Geng;Yanzhi Du
中科院分区：
文献类型：
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作者：
Luwei Jiao;Shang Li;Junyu Zhai;Dongshuang Wang;Hongwanyu Li;Weiwei Chu;Xueying Geng;Yanzhi Du
女性的生殖是由激素精确调节的，而卵巢很容易受到环境内分泌干扰物（EDCs）的影响，而环境内分泌干扰物在工业化社会中无处不在。对羟基苯甲酸酯是一种EDCs，在化妆品、个人护理产品（pcp）、药品和食品中用作抗菌防腐剂。我们使用超高高效液相色谱-质谱法定量检测74名育龄妇女尿液样本中甲基、乙基、丁基和丙基对羟基苯甲酸酯（PP）的浓度。Balb/c小鼠连续21天皮下注射100 mg/kg/天的PP，或在超排卵期皮下注射100、1000 mg/kg/天的PP。在人卵巢颗粒瘤源性细胞系（KGN）培养中加入不同浓度的PP (1 ~ 1000 nM) 24小时。在采集样本前48小时内使用化妆品和其他pcp的女性尿液中对羟基苯甲酸酯浓度显著升高，PP浓度与基础雌二醇浓度显著正相关。注射PP后，小鼠血清雌二醇浓度明显升高，发情周期紊乱，黄体数量减少，取卵细胞数量明显减少。在体外实验中，PP处理增加了雌二醇的合成以及芳香化酶（CYP19A1）和类固醇急性调节蛋白的表达水平。本研究论证了PP对卵巢雌二醇分泌和排卵的不良影响，进一步评价了PP作为防腐剂的安全性，为育龄妇女使用PP和化妆品提供指导。
Female reproduction is precisely regulated by hormones, and the ovary is easily affected by environmental endocrine disruptors (EDCs), which are ubiquitous in industrialized societies. Parabens are EDCs that are used as antibacterial preservatives in cosmetics, personal care products (PCPs), medicines, and food. We used ultrahigh‐performance liquid chromatography–mass spectrometry to quantitatively detect methyl‐, ethyl‐, butyl‐, and propylparaben (PP) concentrations in urine samples from 74 women of childbearing age. Balb/c mice were subcutaneously injected with 100 mg/kg/day of PP for 21 consecutive days or 100 or 1,000 mg/kg/day of PP during superovulation. Various concentrations of PP (ranging from 1 to 1,000 nM) were added to a human ovarian granulosa tumor‐derived cell line (KGN) culture for 24 h. The urinary paraben concentrations of women who used cosmetics and other PCPs within 48 h prior to sample collection were significantly elevated, and the PP concentration was significantly positively correlated with the basal estradiol concentration. After PP injection, the mouse serum estradiol concentrations were significantly increased, estrus cycles were disordered, corpus luteum number was reduced, and number of oocytes retrieved was significantly reduced. In in vitro experiments, PP treatment increased estradiol synthesis and the expression levels of aromatase enzyme (CYP19A1) and steroidogenic acute regulatory protein. This study demonstrates the adverse effects of PP on ovarian estradiol secretion and ovulation, further evaluates the safety of PP as a preservative, and provides guidance for the use of PCPs and cosmetics by women of childbearing age.