Role of JNK and ERK1/2 MAPK signaling pathway in testicular injury of rats induced by di-N-butyl-phthalate (DBP)

Biol Res. 2019 Aug 6;52(1):41. doi: 10.1186/s40659-019-0248-1.

Abstract

Background: Di-N-butyl-phthalate (DBP) is an endocrine disrupting substance. We investigated the adverse effect of DBP on testis of male rat and reveal its potential mechanism of MAPK signaling pathway involved this effect in vivo and in vitro. Gonadal hormone, sperm quality, morphological change and the activation status of JNK, ERK1/2 and p38 was determined in vivo. Primary Sertoli cell was established and cultivated with JNK, ERK1/2 inhibitors, then determine the cell viability, apoptosis and the expression of p-JNK, p-ERK1/2. Data in this study were presented as mean ± SD and determined by one-way analysis of variance (ANOVA) followed by Bonferroni's test. Difference was considered statistically significant at P < 0.05.

Results: In vivo experiment, DBP impaired the normal structure of testicular tissue, reduced testosterone levels in blood serum, decreased sperm count and increased sperm abnormality, p-ERK1/2 and p-JNK in rat testicular tissue increased in a dose-dependent manner. In vitro studies, DBP could decrease the viability of Sertoli cells and increase p-ERK1/2 and p-JNK. Cell apoptosis in SP600125 + DBP group was significantly lower than in DBP group (P < 0.05). p-JNK was not significantly decreased in SP600125 + DBP group, while p-ERK1/2 was significantly decreased in U0126 + DBP group.

Conclusions: These results suggest that DBP can lead to testicular damage and the activation of ERK1/2 and JNK pathways, the JNK signaling pathway may be primarily associated with its effect.

Keywords: Di-N-butyl-phthalate; Mitogen-activated protein kinase; Sertoli cells; Testis.

MeSH terms

  • Animals
  • Dibutyl Phthalate / pharmacology*
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • JNK Mitogen-Activated Protein Kinases / physiology
  • MAP Kinase Signaling System / physiology*
  • Male
  • Mitogen-Activated Protein Kinases / metabolism*
  • Mitogen-Activated Protein Kinases / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / physiology*
  • Testis / drug effects
  • Testis / injuries*
  • Testis / metabolism*

Substances

  • Dibutyl Phthalate
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases