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  2. Preconception exposure to dibutyl phthalate (DBP) impairs spermatogenesis by activating NF-κB/COX-2/RANKL signaling in Sertoli cells

Preconception exposure to dibutyl phthalate (DBP) impairs spermatogenesis by activating NF-κB/COX-2/RANKL signaling in Sertoli cells

  • Toxicology. 2022 May 30;474:153213. doi: 10.1016/j.tox.2022.153213.
Zhiwen Xie 1 Shiwei Liu 2 Shan Hua 1 Lei Wu 2 Yongqing Zhang 1 Yiping Zhu 1 Fei Shi 3 Juntao Jiang 4
Affiliations

Affiliations

  • 1 Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
  • 2 Department of Urology, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai 200080, China.
  • 3 Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. Electronic address: shifei191859@126.com.
  • 4 Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. Electronic address: jjturologist@126.com.
Abstract

Dibutyl phthalate (DBP) is an endocrine disruptor, which causes male reproductive dysfunction in rodents. Previous researches demonstrated that DBP exposure impaired spermatogenesis, however, the molecular mechanism is largely uncovered. In this study, we demonstrated that prenatal exposure to DBP increased receptor activator of nuclear factor-κB ligand (RANKL) expression in seminiferous tubules, especially in Sertoli cells. Western blot and immunofluorescence assays showed that DBP induced up-regulation of RANKL expression in Sertoli cells. Furthermore, experimental data showed that DBP increased COX-2 and p-p65 expression in Sertoli cells and depleting COX-2 and p-p65 by specific inhibitor NS3-98 and BAY117082 could partially abolish DBP induced up-regulation of RANKL. Moreover, the content of RANKL in Sertoli cells was significantly increased after DBP exposure by conducting Enzyme linked immunosorbent assay (ELISA), which promoted spermatogonial stem cells (C18-4 cells) Apoptosis in a paracrine manner. Together, our data demonstrated that a novel mechanism for DBP induced impairment of spermatogenesis by activating NF-κB/COX-2/RANKL signaling in Sertoli cells, and provided a diagnostic and therapeutic target.

Keywords

Dibutyl phthalate; RANKL, NF-κB/COX-2 signaling; Sertoli cells; Spermatogenesis.

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