Team 07: Mechanisms of mammalian post-testicular infertility

Our research focus is on mammalian male fertility. More precisely we are interested in the post-testicular aspects of the acquisition of sperm fertilizing ability in the male that roughly account for 50% of male infertility situations in mammals including human. This essentially covers the epididymal maturation and storage of spermatozoa once they have left the testis. In agreement with classical clinical situations with infertile male patients we have developed three areas of research using transgenic mouse models that mimic the human issues.

Research

One major topic is the maintenance of sperm nucleus integrity and its protection against DNA oxidative damage that are known to affect the fertilization rate, the proper development of embryo and the quality of life of the offspring because of the risk of transmission of an altered male paternal chromosomal moiety.

The second topic concerns the impact that classical metabolic and systemic disorders (such as dyslipidemia and hypercholesterolemia that are very frequent in developed countries) may have on the quality of sperm maturation and consequently on male fertility.

Finally, we also have developed mouse models that allow us to explore the very peculiar immune situation surrounding mature spermatozoa in the epididymis where tolerance towards the immune challenging spermatozoa should be maintained while a robust anti-infectious/anti-inflammatory survey should be installed. This fragile equilibrium is at stake in numerous human male infertility cases.

Selected team publications

Epididymis seleno-independent glutathione peroxidase 5 (GPx5) contributes to the maintenance of sperm DNA integrity. J. Clin. Invest., 119: 2074-2085 (2009).

LXR and ABCA1 control cholesterol homeostasis in the proximal mouse epididymis in a cell specific manner.  J. Lipid. Res., 50:1766-1775 (2009).

Mammalian glutathione peroxidases control acquisition and maintenance of spermatozoa integrity.  J. Anim. Sci., 88(4):1321-1331 (2010).

Deficient-tryptophan catabolism along the kynurenine pathway reveals that the epididymis is in a unique tolerogenic state. J. Biol. Chem., 286(10):8030-8042 (2011).

Dietary cholesterol-induced post-testicular infertility. PloS One. 2011;6(11):e26966. doi: 10.1371/journal.pone.0026966 (2011).

Post-testicular damage to male gametes. The
role of the epididymis.  Med. & Sci,, 28 (5):519-525 (2012).


DNA oxidative damage in mammalian spermatozoa: where and why the male nucleus is impacted? Free Rad. Biol. Med.doi :10.1016/j.freeradbiomed.2013.07.044 (2013).

Research thematics

People

Last Name First Name Position Contact
Stephanie BRAVARD profile picture BRAVARD Stephanie Technical Assistant
Alexandre CHAMPROUX profile picture CHAMPROUX Alexandre Ph.D Student
Christelle DAMON-SOUBEYRAND profile picture DAMON-SOUBEYRAND Christelle Assistant Engineer
Joel DREVET profile picture DREVET Joel Principal Investigator
Chantal GOUBELY profile picture GOUBELY Chantal Engineer
Rachel GUITON profile picture GUITON Rachel Associate Professor
Joelle HENRY-BERGER profile picture HENRY-BERGER Joelle Research Engineer
Ayhan KOCER profile picture KOCER Ayhan Associate Professor
Fabrice SAEZ profile picture SAEZ Fabrice Associate Professor
Allison VOISIN profile picture VOISIN Allison Ph.D Student
Solene VORILHON profile picture VORILHON Solene Ph.D Student
Marjorie WHITFIELD profile picture WHITFIELD Marjorie Ph.D Student

Publications

  • 2017
    • M. Whitfield, R. Guiton, J. Rispal, N. Acar, A. Kocer, J. R. Drevet and F. Saez, “Dyslipidemia alters sperm maturation and capacitation in LXR-null mice.”, Reproduction, 2017.
    • J. R. Drevet, “Sperm DNA integrity testing: a valuable addition to the tool box of infertility clinicians”, Translational Andrology and Urology, vol. 6 (S4) , pp. S590–S591, 2017.
    • H. Nezzar, J. Mbekeani, A. Noblanc, F. Chiambaretta, J. Drevet and A. Kocer, “Investigation of antioxidant systems in human meibomian gland and conjunctival tissues.”, Experimental eye research, vol. 165 , pp. 99–104, 2017.
    • J. T. Carreira, J. T. Trevizan, I. R. Carvalho, B. Kipper, L. H. Rodrigues, C. Silva, S. H. V. Perri, J. R. Drevet and M. B. Koivisto, “Does sperm quality and DNA integrity differ in cryopreserved semen samples from young, adult, and aged Nellore bulls?”, Basic and Clinical Andrology, vol. 27 (1) , 2017.
    • C. Moretti, M. Serrentino, C. Ialy-Radio, M. Delessard, T. A. Soboleva, F. Tores, M. Leduc, P. Nitschké, J. R. Drevet, D. J. Tremethick and e. al., “SLY regulates genes involved in chromatin remodeling and interacts with TBL1XR1 during sperm differentiation”, Cell Death and Differentiation, 2017.
    • C. Chu, L. Yu, B. Wu, L. Ma, L. Gou, M. He, Y. Guo, Z. Li, W. Gao, S. Huijuan, M. Liu, H. Wang, C. Chen, J. Drevet, Y. Zhou and Y. Zhang, “A sequence of 28 S rRNA-derived small RNAs is enriched in mature sperm and various somatic tissues and possibly associates with inflammation.”, Journal of molecular cell biology, 2017.
  • 2016
  • 2015
  • 2014
    • A. Noblanc, A. Kocer and J. R. Drevet, “Recent knowledge concerning mammalian sperm chromatin organization and its potential weaknesses when facing oxidative challenge”, Basic Clin Androl, vol. 24 (1) , pp. 6, 2014.
    • H. Pons-Rejraji, F. Brugnon, B. Sion, S. Maqdasy, G. Gouby, B. Pereira, G. Marceau, A. Gremeau, J. R. Drevet, G. Grizard, L. Janny and I. Tauveron, “Evaluation of atorvastatin efficacy and toxicity on spermatozoa, accessory glands and gonadal hormones of healthy men: a pilot prospective clinical trial.”, Reproductive biology and endocrinology : RB&E, vol. 12 , pp. 65, 2014.
  • 2013
  • 2012
  • 2011
  • 2010
    • A. Jrad-Lamine, J. Henry-Berger, P. Gourbeyre, C. Damon-Soubeyrand, A. Lenoir, L. Combaret, F. Saez, A. Kocer, S. Tone, D. Fuchs, W. Zhu, P. Oefner, D. Munn, A. Mellor, N. Gharbi, R. Cadet, R. Aitken and J. Drevet, “Deficient tryptophan catabolism along the kynurenine pathway reveals that the epididymis is in a unique tolerogenic state.”, J. biol. chem., vol. 286 (10) , pp. 8030–42, 2010.
    • S. Herbette, D. de Labrouhe, J. Drevet and P. Roeckel-Drevet, “Transgenic tomatoes showing higher glutathione peroxydase antioxidant activity are more resistant to an abiotic stress but more susceptible to biotic stresses.”, Plant sci., vol. 180 (3) , pp. 548–53, 2010.
    • F. Saez, A. Ouvrier and J. Drevet, “Epididymis cholesterol homeostasis and sperm fertilizing ability.”, Asian J. Androl., vol. 13 (1) , pp. 11–7, 2010.
  • 2009
    • E. Chabory, C. Damon, A. Lenoir, J. Henry-Berger, P. Vernet, R. Cadet, F. Saez and J. Drevet, “Mammalian glutathione peroxidases control acquisition and maintenance of spermatozoa integrity.”, J. Anim. Sci., vol. 88 (4) , pp. 1321–31, 2009.
    • M. Andre, O. Aumaitre, G. Grateau, M. Chamaillard, N. Costedoat-Chalumeau, M. Cardoso, J. Henry-Berger, B. Ramakrishna, M. Delpech, J. Piette and I. Creveaux, “Longest form of CCTG microsatellite repeat in the promoter of the CD2BP1/PSTPIP1 gene is associated with aseptic abscesses and with Crohn disease in French patients.”, Dig. Dis. Sci., vol. 55 (6) , pp. 1681–8, 2009.
    • E. Chabory, C. Damon, A. Lenoir, G. Kauselmann, H. Kern, B. Zevnik, C. Garrel, F. Saez, R. Cadet, J. Henry-Berger, M. Schoor, U. Gottwald, U. Habenicht, J. Drevet and P. Vernet, “Epididymis seleno-independent glutathione peroxidase 5 maintains sperm DNA integrity in mice.”, J. Clin. Invest., vol. 119 (7) , pp. 2074–85, 2009.
    • H. Pons-Rejraji, B. Sion, F. Saez, F. Brugnon, L. Janny and G. Grizard, “[Role of reactive oxygen species (ROS) on human spermatozoa and male infertility].”, Gynecol Obstet Fertil, vol. 37 (6) , pp. 529–35, 2009.
    • A. Ouvrier, R. Cadet, P. Vernet, B. Laillet, J. Chardigny, JM. Lobaccaro, J. Drevet and F. Saez, “LXR and ABCA1 control cholesterol homeostasis in the proximal mouse epididymis in a cell-specific manner.”, J. Lipid Res., vol. 50 (9) , pp. 1766–75, 2009.
    • A. Ouvrier, R. Cadet, JM. Lobaccaro, J. Drevet and F. Saez, “LXR regulate cholesterol homeostasis in the proximal mouse epididymis.”, Folia Histochem. Cytobiol., vol. 47 (5) , pp. S75–9, 2009.
  • 2008
    • L. Boulanger, A. Kocer, N. Daniel, M. Pannetier, P. Chesne, Y. Heyman, L. Renault, B. Mandon-Pepin, P. Chavatte-Palmer, X. Vignon, J. Vilotte, C. Cotinot, J. Renard and E. Pailhoux, “Attempt to rescue sex-reversal by transgenic expression of the PISRT1 gene in XX PIS-/- goats.”, Sex. Dev., vol. 2 (3) , pp. 142–51, 2008.
    • V. Thimon, G. Frenette, F. Saez, M. Thabet and R. Sullivan, “Protein composition of human epididymosomes collected during surgical vasectomy reversal: a proteomic and genomic approach.”, Hum. Reprod., vol. 23 (8) , pp. 1698–707, 2008.
    • A. Kocer, I. Pinheiro, M. Pannetier, L. Renault, P. Parma, O. Radi, K. Kim, G. Camerino and E. Pailhoux, “R-spondin1 and FOXL2 act into two distinct cellular types during goat ovarian differentiation.”, BMC Dev. Biol., vol. 8 , pp. 36, 2008.
    • N. Dejeans, S. Auclair, J. Henry-Berger, JM. Lobaccaro and A. Mazur, “A specialized cDNA microarray (Mouse Lipid Chip) reveals hepatic overexpression of serum amyloid a in high-fat diet-fed mice.”, Horm. Metab. Res., vol. 40 (3) , pp. 228–30, 2008.
    • T. Zhang, E. Chabory, A. Britan, E. Grignard, O. Pitiot, F. Saez, R. Cadet, J. Henry-Berger, P. Vernet and J. Drevet, “GPX5, the selenium-independent glutathione peroxidase-encoding single copy gene is differentially expressed in mouse epididymis.”, Reprod. Fertil. Dev., vol. 20 (5) , pp. 615–25, 2008.