Exposure to phthalates impaired neurodevelopment through estrogenic effects and induced DNA damage in neurons

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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Author(s)

  • Shisan Xu
  • Huan Zhang
  • Ping-Chieh Pao
  • Audrey Lee
  • Jun Wang
  • Francis A.M. Manno III
  • Shun Wan Chan
  • Xueping Chen

Detail(s)

Original languageEnglish
Article number105469
Journal / PublicationAquatic Toxicology
Volume222
Online published10 Mar 2020
Publication statusPublished - May 2020

Link(s)

Abstract

Phthalates are commonly used in plastic products in daily life. The endocrine-disrupting effects of phthalates have been widely reported. Accumulating evidence from human cohorts and lab animals indicate exposure to phthalates might impair neurodevelopment. However, the direct causal relationship and mechanism between phthalates with neurodevelopment and neurotoxicity have not been firmly established. We found that phthalates (i.e. DBP, DINP, BBP) disrupted the expression of estrogen receptors (esr1, esr2a, esr2b), and impaired neurogenesis in the brain of zebrafish during embryonic development. Moreover, the abnormal expression of estrogen receptors, especially esr2a, was partly rescued in zebrafish which exposed to phthalates, with the estrogen receptor antagonist tamoxifen. Hence, impaired neurogenesis of zebrafish exposed to phthalates was partly reversed by tamoxifen treatment. Moreover, our results show that induced pluripotent stem cells (iPSC)-derived human neurons exposed to phthalates triggered double-strand DNA breaks in vitro. Overall, this study demonstrates that exposure to phthalates affects neurodevelopment in zebrafish embryos and induces neurotoxicity in human neurons partly through disrupting the expression of estrogen receptors.

Research Area(s)

  • Double-Strand DNA break, Estrogen receptor, Estrogenic activity, Neurodevelopment, Neurons, Phthalates, Zebrafish

Citation Format(s)

Exposure to phthalates impaired neurodevelopment through estrogenic effects and induced DNA damage in neurons. / Xu, Shisan; Zhang, Huan; Pao, Ping-Chieh; Lee, Audrey; Wang, Jun; Suen Chan, Yu; Manno III, Francis A.M.; Wan Chan, Shun; Han Cheng, Shuk; Chen, Xueping.

In: Aquatic Toxicology, Vol. 222, 105469, 05.2020.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

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