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n‐ butylparaben induces male reproductive disorders via regulation of estradiol and estrogen receptors
Author(s) -
Zhang Linyuan,
Ding Sijin,
Qiao Peihuan,
Dong Li,
Yu Miao,
Wang Chong,
Zhang Ming,
Zhang Lixia,
Li Yimin,
Tang Ning,
Chang Bing
Publication year - 2016
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3291
Subject(s) - medicine , endocrinology , estrogen receptor , steroidogenic acute regulatory protein , estrogen , aromatase , estrogen receptor alpha , cholesterol side chain cleavage enzyme , biology , offspring , estrogen receptor beta , hormone , androgen receptor , reproductive toxicity , sex steroid , sex hormone receptor , cytochrome p450 , gene expression , pregnancy , steroid , metabolism , toxicity , biochemistry , genetics , cancer , prostate cancer , breast cancer , gene
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 α (ERα) expression was significantly increased and the methylation rate of the ERα 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 ERα, which plays a pivotal role in regulating reproductive and endocrine disorders of male rats exposed to n ‐BP. Furthermore, the epigenetic hypomethylation of ERα 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 © 2016 John Wiley & Sons, Ltd.