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Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
Published on: November 29, 2016
[Testicular injury induced by DBP involved in activation of ERK pathway in KM mice]
Juan Li1, Zhe Wu1, Jian Cheng1
1Department of Internal Medicine, College of Clinical Medicine, Hubei University of Science and Technology, Xianning 437100, China.
Objective:
To investigate the role of extracellular regulated protein kinase( ERK) pathway activation in the testicular injury induced by dibutyl phthalate( DBP) in KM mice.
Methods:
A total of fifty-six male KM mice were randomly divided into 8 groups: control group, 50 mg/( kg·d) DBP group, 50 mg/( kg·d) vitamin E( VE)group, 2 mg/( kg·d) nimodipine( Ni) group, DBP + VE group, DBP + Ni group, Ni +VE group and DBP + Ni + VE group. After consecutive 28 days of treatment, the body weight, testis weight, organ coefficient and sperm density of mice were measured. The histomorphological damage of testis was observed by light microscope. The contents of reactive oxygen species( ROS) and malondialdehyde( MDA) in testicular homogenate of mice in each group were detected by DCFH-DA fluorescence and thiobarbituric acid( TBA) colorimetric method, respectively. The contents of calmodulin( CaM) and level of phosphorylated ERK( p-ERK) were measured by enzyme-linked immunosorbent assay( ELISA).
Results:
Compared with control group, the body weight, testis weight and testicular organ coefficient of mice in 50 mg/( kg·d) DBP group decreased to( 36. 48 ±0. 99) g, ( 0. 25 ± 0. 01) g, ( 0. 54 ± 0. 09) %( P < 0. 05), sperm density decreased to( 11. 70 ± 0. 23) × 10~6/m L( P < 0. 05), and the degree of testicular tissue injury increased with the fluorescence intensity of ROS and the content of MDA increased to( 1698. 18 ± 77. 58), ( 1. 65 ± 0. 13) μmol/g prot( P < 0. 05) respectively. Meanwhile the content of CaM decreased to( 45. 61 ± 2. 69) μg/m L( P < 0. 05) as well as the level of p-ERK increased to( 1150. 43 ± 48. 79) pg/m L( P < 0. 05). After adding VE as antioxidant and Ni as a calcium channel antagonist, compared with 50 mg/( kg·d) DBP group, the body weight and testicular organ coefficient of mice in DBP + Ni + VE group increased to( 40. 69 ± 0. 75) g, ( 0. 69 ± 0. 03) %( P < 0. 05), sperm density increased to( 13. 50 ± 0. 16) × 10~6/m L( P < 0. 05), and the degree of testicular tissue injury decreased with the fluorescence intensity of ROS and the content of MDA decreased to( 1080. 60 ± 98. 64), ( 1. 06 ± 0. 13) μmol/g prot( P < 0. 05) respectively. Meanwhile the content of CaM increased to( 54. 76 ± 1. 74) μg/m L( P < 0. 05) as well as the level of p-ERK decreased to( 904. 55 ± 64. 73) pg/m L( P < 0. 05).
Conclusion:
VE as antioxidant and Ni as calcium channel antagonist can reduce the damage of mouse testicular tissue induced by DBP in varying degrees, suggesting that DBP may activate ERK1/2 pathway through oxidative stress and Ca2 +signal, which may lead to testicular tissue damage in mice.
Insights
Dibutyl phthalate (DBP) exposure causes testicular injury in mice by increasing oxidative stress and activating the ERK pathway. Vitamin E and nimodipine treatments partially reversed these effects, indicating potential therapeutic targets.
Area of Science:
- Toxicology
- Reproductive Biology
- Cell Signaling
Background:
- Environmental toxicants like dibutyl phthalate (DBP) pose risks to reproductive health.
- Extracellular regulated protein kinase (ERK) pathway dysregulation is implicated in various cellular injuries.
Purpose of the Study:
- To investigate the role of extracellular regulated protein kinase (ERK) pathway activation in dibutyl phthalate (DBP)-induced testicular injury in mice.
- To evaluate the protective effects of vitamin E (VE) and nimodipine (Ni) against DBP-induced testicular damage.
Main Methods:
- Male KM mice were administered DBP, VE, Ni, or combinations thereof for 28 days.
- Evaluated body weight, testis weight, organ coefficient, sperm density, and testicular histomorphology.
- Measured reactive oxygen species (ROS), malondialdehyde (MDA), calmodulin (CaM), and phosphorylated ERK (p-ERK) levels.
Main Results:
- DBP exposure significantly decreased body weight, testis weight, organ coefficient, and sperm density while increasing testicular injury, ROS, MDA, and p-ERK levels.
- DBP exposure also decreased CaM levels.
- Co-administration of VE and Ni partially ameliorated DBP-induced testicular damage, reducing ROS and MDA, and normalizing CaM and p-ERK levels.
Conclusions:
- DBP induces testicular injury in mice, potentially via oxidative stress and Ca2+ signaling pathways that activate the ERK1/2 pathway.
- Vitamin E and nimodipine demonstrate protective effects against DBP-induced testicular damage, suggesting therapeutic potential.
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