2. Academic Validation
  3. Transcriptome aberration in mice uterus associated with steroid hormone response and inflammation induced by dioxybenzone and its metabolites

Transcriptome aberration in mice uterus associated with steroid hormone response and inflammation induced by dioxybenzone and its metabolites

  • Environ Pollut. 2021 Oct 1:286:117294. doi: 10.1016/j.envpol.2021.117294.
Tingjie Zhan 1,  Shixuan Cui 1,  Huafeng Shou 2,  Leilei Gao 2,  Shaoyong Lu 3,  Chunlong Zhang 4,  Shulin Zhuang 5
Affiliations

Affiliations

  • 1 Key Laboratory of Environmental Remediation and Ecological Health, Ministry of Education, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058, China.
  • 2 Department of Gynecology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China.
  • 3 Department of Pathophysiology, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China.
  • 4 Department of Environmental Sciences, University of Houston, Clear Lake, TX, 77058, USA.
  • 5 Key Laboratory of Environmental Remediation and Ecological Health, Ministry of Education, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058, China. Electronic address: shulin@zju.edu.cn.
PMID: 33971472 DOI: 10.1016/j.envpol.2021.117294
Abstract

Benzophenone-type UV filters have been implicated in multiple adverse reproductive outcomes, yet the underlying processes and molecular targets on the female reproductive tract remain largely unknown. Herein, we investigated the effect of dioxybenzone, one of the widely used congeners, and its demethylated (M1) and hydroxylated (M2) metabolites on transcriptome profiles of ICR mice uterus and identified potential cellular targets in human endometrial stromal cells (HESCs) separated from normal endometrium tissues. Dioxybenzone, M1 and M2 (20 mg/kg bw/d) significantly induced transcriptome aberration with the induction of 683, 802, and 878 differentially expressed genes mainly involved in Cancer, reproductive system disease and inflammatory disease. Compared to dioxybenzone, M1 and M2 exhibited a transcriptome profile more similar to estradiol in mice uterus, and subsequently promoted thicker endometrial columnar epithelial layer through upregulation of Estrogen Receptor target genes-Sprr2s. Dioxybenzone, M1 and M2 (0.1 or 1 μM) also exhibited estrogenic disrupting effect via increasing the mRNA expressions and production of the growth factors responsible for epithelial proliferation, including Fgfs and Igf-1 in HESCs. Additionally, the mRNA expressions of several inflammatory cytokines especially IL-1β in mice uterus and HESCs was significantly upregulated by dioxybenzone and its metabolites. Overall, we revealed that dioxybenzone and its metabolites triggered transcriptome perturbation dually associated with abnormal steroid hormone response and inflammation, both as key determinants to reproductive health risks.

Keywords

Differentially expressed genes; Endocrine disrupting effect; Reproductive health risk; Toxic pathway; Transcriptome; UV filter.

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