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  3. Multiple transcriptomic profiling: p53 signaling pathway is involved in DEHP-induced prepubertal testicular injury via promoting cell apoptosis and inhibiting cell proliferation of Leydig cells

Multiple transcriptomic profiling: p53 signaling pathway is involved in DEHP-induced prepubertal testicular injury via promoting cell apoptosis and inhibiting cell proliferation of Leydig cells

  • J Hazard Mater. 2021 Mar 15;406:124316. doi: 10.1016/j.jhazmat.2020.124316.
Junke Wang 1,  Tianxin Zhao 2,  Jiadong Chen 2,  Lian Kang 2,  Yuexin Wei 2,  Yuhao Wu 2,  Lindong Han 2,  Lianju Shen 2,  Chunlan Long 2,  Shengde Wu 3,  Guanghui Wei 1
Affiliations

Affiliations

  • 1 Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, PR China; National Clinical Research Center for Child Health and Disorders, Chongqing 400014, PR China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, PR China; Chongqing Key Laboratory of Pediatrics, Chongqing 400014, PR China.
  • 2 Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, PR China; National Clinical Research Center for Child Health and Disorders, Chongqing 400014, PR China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, PR China; Chongqing Key Laboratory of Pediatrics, Chongqing 400014, PR China.
  • 3 Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing 400014, PR China; National Clinical Research Center for Child Health and Disorders, Chongqing 400014, PR China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing 400014, PR China; Chongqing Key Laboratory of Pediatrics, Chongqing 400014, PR China. Electronic address: shengdewu@hospital.cqmu.edu.cn.
PMID: 33162236 DOI: 10.1016/j.jhazmat.2020.124316
Abstract

Di(2-ethylhexyl) phthalate (DEHP) is a widely-used plasticizer and has long been recognized as an endocrine-disrupting chemical with male reproductive toxicities. DEHP exposure at the prepubertal stage may lead to extensive testicular injury. However, the underlying mechanisms remain to be elucidated. In the present study, we gavaged male C57BL/6 mice with different concentrations of DEHP (0, 250, and 500 mg/kg-bw·d) from postnatal day 22-35, and exposed TM3 Leydig cells with 0, 100, 200, 300, and 400 μM of MEHP (bioactive metabolite of DEHP) for 12-48 h. RNA sequencing was performed both in testicular tissue and TM3 cells. The results showed that DEHP disrupts testicular development and reduces serum testosterone levels in male prepubertal mice. Bioinformatic analysis and experimental verification have revealed that DEHP/MEHP induces cell cycle arrest in TM3 cells and increases Apoptosis both in vivo and in vitro. Furthermore, the p53 signaling pathway was found to be activated upon DEHP/MEHP treatment. The inhibition of p53 by pifithrin-α significantly reduced MEHP-induced injuries in TM3 cells. Cumulatively, these findings revealed the involvement of the p53 signaling pathway in DEHP-induced prepubertal testicular injury by promoting cell Apoptosis and inhibiting cell proliferation of Leydig cells.

Keywords

Apoptosis; Cell cycle arrest; Di(2-ethylhexyl) phthalate; Leydig cells; Prepubertal testes; p53.

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