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Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Mitochondrial ferritin deficiency reduces male fertility in mice

Federica Maccarinelli A , Maria Regoni A , Fernando Carmona A , Maura Poli A , Esther G. Meyron-Holtz A B and Paolo Arosio A C
+ Author Affiliations
- Author Affiliations

A Molecular Biology Laboratory, Department of Molecular and Translational Medicine DMMT, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.

B Laboratory for Molecular Nutrition, Faculty of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Technion City, 32000 Haifa, Israel.

C Corresponding author. Email: paolo.arosio@unibs.it

Reproduction, Fertility and Development 29(10) 2005-2010 https://doi.org/10.1071/RD16348
Submitted: 20 July 2016  Accepted: 3 December 2016   Published: 9 January 2017

Abstract

Mitochondrial ferritin (FtMt) is a functional ferritin targeted to mitochondria that is highly expressed in the testis. To investigate the role of FtMt in the testis we set up a series of controlled matings between FtMt gene-deletion mice (FtMt–/–) with FtMt+/+ mice. We found that the number of newborns per litter and the fertility rate were strongly reduced for the FtMt–/– males, but not for the females, indicating that FtMt has an important role for male fertility. The morphology of the testis and of the spermatozoa of FtMt–/– mice was normal and we did not detect alterations in sperm parameters or in oxidative stress indices. In contrast, we observed that the cauda epididymides of FtMt–/– mice were significantly lighter and contained a lower number of spermatozoa compared with the controls. Also, the ATP content of FtMt–/– spermatozoa was found to be lower than that of FtMt+/+ spermatozoa. These data show that FtMt contributes to sperm epididymis maturation and to male fertility.

Additional keywords: ATP, spermatogenesis, sperm motility.


References

Arama, E., Bader, M., Srivastava, M., Bergmann, A., and Steller, H. (2006). The two Drosophila cytochrome C proteins can function in both respiration and caspase activation. EMBO J. 25, 232–243.
The two Drosophila cytochrome C proteins can function in both respiration and caspase activation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xis1Kgsg%3D%3D&md5=3ca27375009610cec0415dd6c68062ecCAS |

Arosio, P., and Levi, S. (2010). Cytosolic and mitochondrial ferritins in the regulation of cellular iron homeostasis and oxidative damage. Biochim. Biophys. Acta 1800, 783–792.
Cytosolic and mitochondrial ferritins in the regulation of cellular iron homeostasis and oxidative damage.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXnvVyhtbs%3D&md5=3bc395cec841777b5a581bd05a9fbecdCAS |

Bartnikas, T. B., Campagna, D. R., Antiochos, B., Mulhern, H., Pondarré, C., and Fleming, M. D. (2010). Characterization of mitochondrial ferritin-deficient mice. Am. J. Hematol. 85, 958–960.
Characterization of mitochondrial ferritin-deficient mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhs1Wktg%3D%3D&md5=4244928c5d84ea14287dfe4e5a8afea8CAS |

Behrouzi, B., Kenigsberg, S., Alladin, N., Swanson, S., Zicherman, J., Hong, S. H., Moskovtsev, S. I., and Librach, C. L. (2013). Evaluation of potential protein biomarkers in patients with high sperm DNA damage. Syst. Biol. Reprod. Med. 59, 153–163.
Evaluation of potential protein biomarkers in patients with high sperm DNA damage.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXntVymt7g%3D&md5=23b8e8ab9cb7c2a116427bf3a2ff4c7bCAS |

Calzi, F., Levi, S., Santambrogio, P., De Santis, L., Rabellotti, E., and Bonzi, V. (2003). Spermatozoa mitochondrial ferritin (MtF) content is related to sperm motility. Fertil. Steril. 80, 31.
Spermatozoa mitochondrial ferritin (MtF) content is related to sperm motility.Crossref | GoogleScholarGoogle Scholar |

Campanella, A., Rovelli, E., Santambrogio, P., Cozzi, A., Taroni, F., and Levi, S. (2009). Mitochondrial ferritin limits oxidative damage regulating mitochondrial iron availability: hypothesis for a protective role in Friedreich ataxia. Hum. Mol. Genet. 18, 1–11.
Mitochondrial ferritin limits oxidative damage regulating mitochondrial iron availability: hypothesis for a protective role in Friedreich ataxia.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhsV2lurrM&md5=dc8ee1173b69d801c210facf28204d05CAS |

Cavadini, P., Biasiotto, G., Poli, M., Levi, S., Verardi, R., Zanella, I., Derosas, M., Ingrassia, R., Corrado, M., and Arosio, P. (2007). RNA silencing of the mitochondrial ABCB7 transporter in HeLa cells causes an iron-deficient phenotype with mitochondrial iron overload. Blood 109, 3552–3559.
RNA silencing of the mitochondrial ABCB7 transporter in HeLa cells causes an iron-deficient phenotype with mitochondrial iron overload.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXksFWhs7k%3D&md5=1900afc99c323a89dc12bc6af102cca2CAS |

Hales, K. G., and Fuller, M. T. (1997). Developmentally regulated mitochondrial fusion mediated by a conserved, novel, predicted GTPase. Cell 90, 121–129.
Developmentally regulated mitochondrial fusion mediated by a conserved, novel, predicted GTPase.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXkslSgsro%3D&md5=ff36e56a93a08c5ea811c635d8f4041aCAS |

Leichtmann-Bardoogo, Y., Cohen, L. A., Weiss, A., Marohn, B., Schubert, S., Meinhardt, A., and Meyron-Holtz, E. G. (2012). Compartmentalization and regulation of iron metabolism proteins protect male germ cells from iron overload. Am. J. Physiol. Endocrinol. Metab. 302, E1519–E1530.
Compartmentalization and regulation of iron metabolism proteins protect male germ cells from iron overload.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtVGlsrzL&md5=e2f930e1986031a216b14eb7415b4274CAS |

Levi, S., and Arosio, P. (2004). Mitochondrial ferritin. Int. J. Biochem. Cell Biol. 36, 1887–1889.
Mitochondrial ferritin.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXltVKhsbs%3D&md5=839fd3208e245c66076f7875b2d99cc6CAS |

Maccarinelli, F., Gammella, E., Asperti, M., Regoni, M., Biasiotto, G., Turco, E., Altruda, F., Lonardi, S., Cornaghi, L., Donetti, E., Recalcati, S., Poli, M., Finazzi, D., Arosio, P., and Cairo, G. (2014). Mice lacking mitochondrial ferritin are more sensitive to doxorubicin-mediated cardiotoxicity. J. Mol. Med. 92, 859–869.
Mice lacking mitochondrial ferritin are more sensitive to doxorubicin-mediated cardiotoxicity.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXms1Cgtbo%3D&md5=80c6f962ddd444e1ed076c95f159b197CAS |

Metzendorf, C., and Lind, M. I. (2010). Drosophila mitoferrin is essential for male fertility: evidence for a role of mitochondrial iron metabolism during spermatogenesis. BMC Dev. Biol. 10, 68.
Drosophila mitoferrin is essential for male fertility: evidence for a role of mitochondrial iron metabolism during spermatogenesis.Crossref | GoogleScholarGoogle Scholar |

Orlando, C., Caldini, A. L., Barni, T., Wood, W. G., Strasburger, C. J., Natali, A., Maver, A., Forti, G., and Serio, M. (1985). Ceruloplasmin and transferrin in human seminal plasma: are they an index of seminiferous tubular function? Fertil. Steril. 43, 290–294.
Ceruloplasmin and transferrin in human seminal plasma: are they an index of seminiferous tubular function?Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2M7gt1WrsA%3D%3D&md5=fd071b2def2d37520b56bd457919d8d4CAS |

Perera, D., Pizzey, A., Campbell, A., Katz, M., Porter, J., Petrou, M., Irvine, D. S., and Chatterjee, R. (2002). Sperm DNA damage in potentially fertile homozygous beta-thalassaemia patients with iron overload. Hum. Reprod. 17, 1820–1825.
Sperm DNA damage in potentially fertile homozygous beta-thalassaemia patients with iron overload.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xmt1Glsbg%3D&md5=a20055827661987cabe99e12bf421027CAS |

Santambrogio, P., Biasiotto, G., Sanvito, F., Olivieri, S., Arosio, P., and Levi, S. (2007). Mitochondrial ferritin expression in adult mouse tissues. J. Histochem. Cytochem. 55, 1129–1137.
Mitochondrial ferritin expression in adult mouse tissues.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXht1aju73L&md5=374b81cd2031548c91caa7f4f1a75edcCAS |

Skinner, M. K., and Griswold, M. D. (1980). Sertoli cells synthesize and secrete transferrin-like protein. J. Biol. Chem. 255, 9523–9525.
| 1:CAS:528:DyaL3cXls1GisLg%3D&md5=c1a9f32c5ef980a12a2950a317e67eefCAS |