n-butylparaben induces male reproductive disorders via regulation of estradiol and estrogen receptors

作者：Zhang Linyuan; Ding Sijin; Qiao Peihuan; Dong Li; Yu Miao; Wang Chong; Zhang Ming; Zhang Lixia; Li Yimin; Tang Ning; Chang Bing^*

来源：Journal of Applied Toxicology, 2016, 36(9): 1223-1234.

DOI：10.1002/jat.3291

• endocrine disruptors
• estrogen receptors
• steroidogenesis
• testis
• DNA methylation

It is well known that inappropriate exposure to exogenous hormones during fetal or neonatal life, such as testosterone (T) and estradiol (E-2), leads to adverse reproductive outcomes. In our previous study, the reproductive dysfunction of male rats was characterized by an E-2 increase and T decrease after in utero and lactation exposures to n-butylparaben (n-BP). In this study, we investigated the synthesis and metabolism pathways of steroid hormones, hormone receptors and the epigenetic modification of male offspring on postnatal day (PND) 21 and PND90 to explore the possible mechanisms of endocrine and reproductive disorders. The expression of steroidogenic acute regulatory protein (StAR), cytochrome cholesterol side-chain cleavage enzyme (P450scc), estrogen sulfotransferase (SULT1E1) and androgen receptor (AR) in the testes was significantly decreased at the transcript and protein levels; in addition, aromatase (CYP19) and estrogen receptor (ER) expression was significantly increased and the methylation rate of the ER promoter was significantly decreased. These results suggest that increased CYP19 expression and decreased SULT1E1 expression are responsible for the E-2 increase. This effect promotes the expression of ER, which plays a pivotal role in regulating reproductive and endocrine disorders of male rats exposed to n-BP. Furthermore, the epigenetic hypomethylation of ER is involved in this regulation processes. Our study is the first to report on the possible mechanism of male rat reproductive disorders induced by the xenoestrogenic chemical n-BP. Copyright (c) 2016 John Wiley & Sons, Ltd.
Exposure to exogenous hormones during fetal or neonatal life leads to adverse reproductive outcomes. In this study, we investigated the possible mechanisms of reproductive disorders induced by n-butylparaben in utero and lactation in rats, which indicated that altered synthesis and metabolism of T and E-2, the expressions of ER and epigenetic hypomethylation of ER contributed to the reproductive disorders. It is the first time to elucidate the possible mechanisms of reproductive disorders induced by n-butylparaben as a xenoestrogenic chemical.

• 出版日期2016-9
• 单位中国疾病预防控制中心; 中国疾病预防控制中心职业卫生与中毒控制所