Exposure to N-monoacetyl-p-phenylenediamine impaired ovarian function in mice
Exposure to N-monoacetyl-p-phenylenediamine impaired ovarian function in mice
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暴露于 N-单乙酰基-对苯二胺会损害小鼠卵巢功能
DOI：
10.1002/jat.4183
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发表时间：
2021-05-20
影响因子：
3.3
通讯作者：
Liu，Xueqing
中科院分区：
文献类型：
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作者：
Yu，Liliang;Zhai，Jingwei;Liu，Xueqing
对苯二胺（PPD）是永久性染发剂的主要成分，也广泛用于摄影和橡胶工业。PPD及其代谢物已被证明会增加癌症（特别是卵巢癌）的风险;然而，它们对女性生殖的影响尚不清楚。我们研究了PPD代谢产物N-单乙酰基-PPD（MAPPD）对小鼠囊胚发育和卵巢功能的影响。以0、100和300 mg/kg/天MPPD剂量对60只8周龄雌性昆明小鼠灌胃给药28天。用浓度为0、50、100和300 μg/ml的MAPPD处理KGN（人卵巢颗粒细胞）48 h。在所有给药组中，妊娠第3.5天异常囊胚数量增加。与对照组相比，MAPPD暴露组有腔卵泡数量减少，卵巢组织E2、P4水平下降，血清E2、P4、促黄体生成素（LH）、T水平下降，促卵泡激素（FSH）升高。FSH受体（FSHR）和LH受体（LHR）表达显著下调，氧化应激水平显著升高。在KGN细胞中，活性氧水平以剂量依赖性方式增加，FSHR，LHR和芳香化酶的mRNA水平增加。这些结果表明，MAPPD通过引起氧化应激抑制FSH和LH诱导的芳香化酶活性，从而降低激素水平，导致卵泡发育异常。同时，MAPPD暴露可通过影响卵子质量而影响早期胚胎发育异常。
p‐Phenylenediamine (PPD) is the main constituent of permanent hair dye and is also widely used in the photographic and rubber industries. PPD and its metabolites have been shown to increase the risk of cancer (especially ovarian cancer); however, their effect on female reproduction is unclear. We investigated the effects of the PPD metaboliteN‐monoacetyl‐PPD (MAPPD) on mouse blastocyst development and ovarian function. Sixty 8‐week‐old female Kunming mice were administered at 0‐, 100‐, and 300‐mg/kg/day MPPD by gavage for 28 days. KGN (human ovarian granulosa cells) were treated with MAPPD at concentrations of 0, 50, 100, and 300 μg/ml for 48 h. The number of abnormal blastocysts increased on gestation day 3.5 in all treatment groups. Compared with the control group, in MAPPD exposed group, the number of antral follicles decreased, the levels of E2and P4decreased in ovarian tissue, the serum levels of E2, P4, luteinizing hormone (LH), and T decreased, and follicle‐stimulating hormone (FSH) increased. The expression of FSH receptor (FSHR) and LH receptor (LHR) was significantly downregulated, and the level of oxidative stress was significantly increased. In KGN cells, the level of reactive oxygen species increased in a dose‐dependent manner, and the mRNA levels of FSHR, LHR, and aromatase increased. These results suggest that MAPPD inhibits FSH‐ and LH‐induced aromatase activity by causing oxidative stress, which decrease hormone levels, leading to abnormal follicle development. Meanwhile, MAPPD exposure could affect early embryonic development abnormalities by affecting the quality of ovum.