title: n-butylparaben induces male reproductive disorders via regulation of estradiol and estrogen receptors.
abstract: It is well known that inappropriate exposure to exogenous hormones during fetal or neonatal life, such as testosterone (T) and estradiol (E2), leads to adverse reproductive outcomes. In our previous study, the reproductive dysfunction of male rats was characterized by an E2increase 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 E2increase. 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.
authors.affiliation: Key Laboratory of Chemical Safety and Health, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, No. 29 Nanwei Road, Xicheng district, Beijing, 100050, China.
authors.forename: Linyuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Chemical Safety and Health, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, No. 29 Nanwei Road, Xicheng district, Beijing, 100050, China.
authors.forename: Sijin
authors.initials: S
authors.lastname: Ding
authors.affiliation: Key Laboratory of Chemical Safety and Health, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, No. 29 Nanwei Road, Xicheng district, Beijing, 100050, China.
authors.forename: Peihuan
authors.initials: P
authors.lastname: Qiao
authors.affiliation: Department of Environmental Toxicology, Institute of Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, No. 7 Panjiayuan nanli, Chaoyang district, Beijing, 100021, China.
authors.forename: Li
authors.initials: L
authors.lastname: Dong
authors.affiliation: Key Laboratory of Chemical Safety and Health, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, No. 29 Nanwei Road, Xicheng district, Beijing, 100050, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Environmental Toxicology, Institute of Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, No. 7 Panjiayuan nanli, Chaoyang district, Beijing, 100021, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Environmental Toxicology, Institute of Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, No. 7 Panjiayuan nanli, Chaoyang district, Beijing, 100021, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Environmental Toxicology, Institute of Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, No. 7 Panjiayuan nanli, Chaoyang district, Beijing, 100021, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Environmental Toxicology, Institute of Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, No. 7 Panjiayuan nanli, Chaoyang district, Beijing, 100021, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Environmental Toxicology, Institute of Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, No. 7 Panjiayuan nanli, Chaoyang district, Beijing, 100021, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Tang
authors.affiliation: Key Laboratory of Chemical Safety and Health, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, No. 29 Nanwei Road, Xicheng district, Beijing, 100050, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Chang
keywords: DNA methylation; endocrine disruptors; estrogen receptors; steroidogenesis; testis