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Effects of Fluoride on Expression of P450, CREM and ACT Proteins in Rat Testes

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Abstract

Fluoride (F) is an essential trace element that humans and animals ingest from water, air, and fluoride-containing products; however, excessive fluoride absorption can damage a variety of organs and tissues, including the male reproductive system. Our previous studies found that fluoride exposure lowered sperm quality and interfered with spermatogenesis; however, the exact mechanism remained unclear. Proteins cytochrome P450 (P450), cAMP-responsive element modulator (CREM), and activator of CREM in testis (ACT) play the key roles in spermatogenesis and sperm motility. To investigate whether fluoride affects the expression of P450, CREM, and ACT, we used immunohistochemical techniques to determine expression levels of these proteins in testes of rats administered 100 mg NaF/L for 2 weeks via drinking water. The results showed that P450 expression was decreased while CREM and ACT expression was increased in the fluoride group, compared to the control. These data suggest that fluoride can impair male reproduction by affecting expression of P450, CREM, and ACT in the testes.

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References

  1. Agalakova NI, Gusev G.P. (2012) Molecular mechanisms of cytotoxicity and apoptosis induced by inorganic fluoride. ISRN Cell Biology:1–16

  2. Wan SX, Zhang JH, Wang JD (2006) Effects of high fluoride on sperm quality and testicular histology in male rats. Fluoride 39(1):17–21

    CAS  Google Scholar 

  3. Zhang S, Jiang C, Liu H et al (2013) Fluoride-elicited developmental testicular toxicity in rats: roles of endoplasmic reticulum stress and inflammatory response. Toxicol Appl Pharmacol 271(2):206–215

    Article  CAS  PubMed  Google Scholar 

  4. Yan XY, Hao XH, Nie QL et al (2015) Effects of fluoride on the ultrastructure and expression of Type I collagen in rat hard tissue. Chemosphere 128:36–41

    Article  CAS  PubMed  Google Scholar 

  5. Zhou B, Zhao J, Liu J et al (2015) Fluoride-induced oxidative stress is involved in the morphological damage and dysfunction of liver in female mice. Chemosphere 139:504–511

    Article  CAS  PubMed  Google Scholar 

  6. Xu H, Hu LS, Chang M et al (2005) Proteomic analysis of kidney in fluoride-treated rat. Toxicol Lett 160(1):69–75

    Article  CAS  PubMed  Google Scholar 

  7. Niu RY, Liu SL, Wang JM et al (2014) Proteomic analysis of hippocampus in offspring male mice exposed to fluoride and lead. Biol Trace Elem Res 162(1–3):227–233

    Article  CAS  PubMed  Google Scholar 

  8. GeY NR, Zhang J et al (2011) Proteomic analysis of brain proteins of rats exposed to high fluoride and low iodine. Arch Toxicol 85(1):27–33

    Article  Google Scholar 

  9. Zhou BH, Wang HW, Wang JM et al (2007) Effects of malnutrition and supplemented nutrition on non-specific immune function changes induced by fluoride in rabbits. Fluoride 40(3):169–177

    CAS  Google Scholar 

  10. Barbier O, Arreola-Mendoza L, Del Razo LM (2010) Molecular mechanisms of fluoride toxicity. Chem Biol Interact 188:319–333

    Article  CAS  PubMed  Google Scholar 

  11. Long H, Jin Y, Lin M et al (2009) Fluoride toxicity in the male reproductive system. Fluoride 42(3):260–276

    CAS  Google Scholar 

  12. Zhang JH, Liang C, Ma JJ et al (2006) Effects of sodium fluoride and sulfur dioxide on sperm motility and serum testosterone in male rats. Fluoride 39(2):126–131

    CAS  Google Scholar 

  13. Wan SX, Zhang JH, Wang JD (2006) Fluoride-induced changes in the expression of epidermal growth factor and its receptor in testicular tissues of young male rats. Fluoride 39(2):121–125

    CAS  Google Scholar 

  14. Sun ZL, Zhang W, Xue XC et al (2016) Fluoride decreased the sperm ATP of mice through inhabiting mitochondrial respiration. Chemosphere 144:1012–1017

    Article  CAS  PubMed  Google Scholar 

  15. Lu ZJ, Wang SL, Sun ZL et al (2014) In vivo influence of sodium fluoride on sperm chemotaxis in male mice. Arch Toxicol 88:533–539

    Article  CAS  PubMed  Google Scholar 

  16. Han HJ, Sun ZL, Luo GY et al (2015) Fluoride exposure changed the structure and the expressions of reproductive related genes in the hypothalamus-pituitary-testicular axis of male mice. Chemosphere 135:297–303

    Article  CAS  PubMed  Google Scholar 

  17. Cheshenko K, Pakdel F, Segner H et al (2008) Interference of endocrine disrupting chemicals with aromatase CYP19 expression or activity, and consequences for reproduction of teleost fish. Gen Comp Endocrinol 155:31–62

    Article  CAS  PubMed  Google Scholar 

  18. Hinfray N, Porcher JM, Brion F (2006) Inhibition of rainbow trout (Oncorhynchus mykiss) P450 aromatase activities in brain and ovarian microsomes by various environmental substances. Comp Biochem Physiol C: Toxicol Pharmacol 144:252–262

    Google Scholar 

  19. Sassone-Corsi P (2000) CREM: a master-switch regulating the balance between differentiation and apoptosis in male germ cells. Mol Reprod Dev 56:228–229

    Article  CAS  PubMed  Google Scholar 

  20. Kotaja N, Macho B, Sassone-Corsi P (2005) Microtubule-independent and protein kinase A-mediated function of kinesin KIF17b controls the intracellular transport of activator of CREM in testis (ACT). J Biol Chem 280:31739–31745

    Article  CAS  PubMed  Google Scholar 

  21. Olivier B, Laura AM, Del Razo LM (2010) Molecular mechanisms of fluoride toxicity. Chem Biol Interact 188(2):319–333

    Article  Google Scholar 

  22. Ortiz-Perez D, Rodríguez-Martínez M, Martínez F et al (2003) Fluoride-induced disruption of reproductive hormones in men. Environ Res 93:20–30

    Article  CAS  PubMed  Google Scholar 

  23. Danielson PB (2002) The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans. Curr Drug Metab 3:561–597

    Article  CAS  PubMed  Google Scholar 

  24. Miller W (1988) Molecular biology of steroid hormone synthesis. Endocr Rev 9:295–318

    Article  CAS  PubMed  Google Scholar 

  25. Ijiri S, Takei N, Kazeto Y (2006) Changes in localization of cytochrome P450 cholesterol side-chain cleavage (P450scc) in Japanese eel testis and ovary during gonadal development. Gen Comp Endocrinol 145:75–83

    Article  CAS  PubMed  Google Scholar 

  26. Hinfray N, Baudiffier D, Marcelo C et al (2011) Characterization of testicular expression of P450 17α-hydroxylase, 17,20-lyase in zebrafish and its perturbation by the pharmaceutical fungicide clotrimazole. Gen Comp Endocrinol 174:309–317

    Article  CAS  PubMed  Google Scholar 

  27. Carpino A, Pezzi V, Rago V et al (2001) Immunolocalization of cytochrome P450 aromatase in rat testis during postnatal development. Tissue Cell 33(4):349–353

    Article  CAS  PubMed  Google Scholar 

  28. Nantel F, Monaco L, Foulkes NS (1996) Spermiogenesis deficiency and germ-cell apoptosis in CREM-mutant mice. Nature 380:159

    Article  CAS  PubMed  Google Scholar 

  29. Krausz C, Sassone-Corsi P (2005) Genetic control of spermiogenesis: insights from the CREM gene and implications for human infertility. Reprod Biomnd Online 10:64–71

    Article  CAS  Google Scholar 

  30. Fimia GM, De Cesare D, Sassone-Corsi P (1999) CBP-independent activation of CREM and CREB by the LIM-only protein ACT. Nature 398:165–169

    Article  CAS  PubMed  Google Scholar 

  31. Yu YE, Yun Z, Emmanual U et al (2000) Abnormal spermatogenesis and reduced fertility in transition nuclear protein 1-deficient mice. PNAS 97:4683–4688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Dadoune JP (2003) Expression of mammalian spermatozoal nucleo-proteins. Microsc Res Tech 61:56–75

    Article  CAS  PubMed  Google Scholar 

  33. Beißbarth T, Borisevich I, Hörlein A (2003) Analysis of CREM-dependent gene expression during mouse spermatogenesis. Mol Cell Endocrinol 212:29–39

    Article  PubMed  Google Scholar 

  34. Kotaja N, De Cesare D, Macho B et al (2004) Abnormal sperm in mice with targeted deletion of the act (activator of Camp-responsive element modulator in testis) gene. PNAS 101:10620–10625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This research was supported by the China National Natural Science Foundation (Grant No. 30901092, 31172380), Specialized Research Fund for the Doctoral Program of Higher Education of China (20091403120002), Science and Technology Program of Shanxi Province (20130311028–4), Program for Top Young Academic Leaders of Higher Institutions of Shanxi (201001), and Program for Innovation of Outstanding Graduate in Shanxi Province (2014057).

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Authors and Affiliations

  1. Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, China

    Jianhai Zhang, Yuchen Zhu, Chen Liang, Mingli Qie, Ruiyan Niu, Zilong Sun, Jinming Wang & Jundong Wang

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  1. Jianhai Zhang
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  2. Yuchen Zhu
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  3. Chen Liang
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  4. Mingli Qie
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  5. Ruiyan Niu
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  6. Zilong Sun
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  7. Jinming Wang
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Correspondence to Jianhai Zhang or Jundong Wang.

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All regulations of the Institutional Animal Care and Use Committee of Shanxi Agricultural University were strictly followed during the experiment to protect the welfare of the animals.

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The authors declare that they have no conflicts of interest.

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Zhang, J., Zhu, Y., Liang, C. et al. Effects of Fluoride on Expression of P450, CREM and ACT Proteins in Rat Testes. Biol Trace Elem Res 175, 156–160 (2017). https://doi.org/10.1007/s12011-016-0753-9

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  • DOI: https://doi.org/10.1007/s12011-016-0753-9

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