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Oxidative Stress, Inflammatory Reactions and Apoptosis Mediated the Negative Effect of Chronic Stress Induced by Maternal Separation on the Reproductive System in Male Mice Publisher Pubmed



Khodamoradi K1 ; Aminikhoei H2 ; Khosravizadeh Z1 ; Hosseini SR3 ; Dehpour AR4, 5 ; Hassanzadeh G1
Authors
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Authors Affiliations
  1. 1. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
  3. 3. Departent of Urology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Reproductive Biology Published:2019


Abstract

Exposure to severe and long-lasting stressors during early postnatal life negatively affects development of the brain and associated biological networks. Maternal separation (MS) is a valid stressful experience in early life that adversely affects neurobiological circuits. In the present study, we aimed to evaluate the effects of MS on sperm quality and histology of the testis in adult male mice. In this study, male mice were subjected to MS during post-natal days (PND) 2–14. Sperm parameters, histological alterations in the testicular tissue, ROS production (using DCFH-DA assay), gene expression of TLR4, NLRP3, TNFα, BAX, ASC, caspase-1 and BCL-2 (using RT-PCR), protein levels of caspase-3 and caspase-8 (using western blotting), and protein levels of IL-1β, IL-18, GPx and ATP (using ELISA) as well as protein expression of caspase-1 and NLRP3 (using immunocytochemistry) were evaluated. Findings showed that MS decreased count, morphology and viability of spermatozoa. MS decreased the diameter of seminiferous tubules and decreased the thickness of seminiferous epithelium. Furthermore, MS increased the level of ROS production and decreased the concentrations of GPx and ATP. MS led to increased expression of TLR4, NlRP3, TNFα, caspase-1, ASC, IL-1β and IL-18. In addition, MS induced apoptosis as evidenced by increased BAX, caspase-3 and caspase-8 as well as decreased BCL-2 expression. We concluded that early life stress induced by MS has detrimental effects on sperm parameters and testicular tissue. Our results suggest that these effects are mediated by activation of ROS production, and alterations in mitochondrial function, inflammatory processes and apoptosis pathways. © 2019 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn
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