Volume 24, Issue 105, September - October, 2020

Exposure to bis (2-ethylhexyl) phthalate causes sperm quality deteriorations, oxidative stress and down-regulates the expression of Catsper2 gene and protein in testis of mice

Shabnam Mohammadi^1,2♦, Seyed Mehdi Hasanian³, Farzad Rahmani³, Mahsa Akbari Oryani⁴, Mehdi Jalali¹, Farimah Beheshti⁵, Parisa Haeri¹

¹Department of Anatomy and Cell Biology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
²Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
³Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
⁴Department of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
⁵Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

^♦Corresponding author
Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Email: mohammadish@mums.ac.ir

ABSTRACT

Purpose: Environmental factors such as exposure to heavy metals and air pollutants are factors influencing the male fertility. The present study was conducted to determine the effect of bis (2-ethylhexyl) phthalate administration on sperm parameters, testicular histopathology, expression of Catsper2 gene and protein and oxidative stress in male adult mice. Methods: In this study, 32 male NMRI mice were randomly divided into 4 groups of control and phthalate 1-3. The control group received the solvent of bis(2- ethylhexyl) phthalate (corn oil). The phthalate 1-3 groups received 50, 250, and 500 mg/kg of bis(2-ethylhexyl) phthalate for 14 days, respectively. Sperm, CatSper2 gene and protein expression, testicular histopathology and oxidative stress assessments were performed 5 weeks after the intervention. Results: Our results showed that, the administration of phthalate reduced sperm parameters as well as interstitial space and congestion with incomplete spermatogenesis in seminiferous tubules. Mice received phthalate showed a significant decrease in CatSper2 gene expression compared to the controls (p<0.05). The changes identified in CatSper2 protein expression levels were consistent with their relative mRNA level. A significant difference was found in the mean levels of malondialdehyde and superoxide dismutase enzyme between the phthalate 2 and 3 groups and the control group. A significant increase was observed in the mean thiol level in phthalate 1 (p = 0.04), phthalate 2 (p<0.001) and phthalate 3 (p<0.001) groups compared to the control group. Conclusion: The exposure to bis(2-ethylhexyl) phthalate reduces sperm quality especially sperm with tail defects and degenerative changes in testicular tissue and increases oxidative stress in male mice. A dose-dependent reduction was also observed in CatSper gene and protein expression.

Keywords: Phthalate; CatSper; Sperm; Testis; Mice

Medical Science, 2020, 24(105), 3128-3136

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