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.

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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
Areski CHORFA profile picture CHORFA Areski Engineer
Christelle DAMON-SOUBEYRAND profile picture DAMON-SOUBEYRAND Christelle Assistant Engineer
Joel DREVET profile picture DREVET Joel Principal Investigator
Fatima EL IT profile picture EL IT Fatima Intern
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
Kevin POISSENOT profile picture POISSENOT Kevin Ph.D Student
Fabrice SAEZ profile picture SAEZ Fabrice Associate Professor

Publications

  • 2020
    • A. Voisin, C. Damon-Soubeyrand, S. Bravard, F. Saez, J. Drevet and R. Guiton, “Differential expression and localisation of TGF-beta isoforms and receptors in the murine epididymis.”, Scientific reports, vol. 10 (1) , pp. 995, 2020.
    • J. Drevet and R. Aitken, “Oxidation of Sperm Nucleus in Mammals: A Physiological Necessity to Some Extent with Adverse Impacts on Oocyte and Offspring.”, Antioxidants (Basel, Switzerland), vol. 9 (2) , 2020.
  • 2019
    • M. Mousavi, A. Shahverdi, J. Drevet, V. Akbarinejad, V. Esmaeili, F. Sayahpour, T. Topraggaleh, P. Rahimizadeh and A. Alizadeh, “Peroxisome Proliferator-Activated Receptors (PPARs) levels in spermatozoa of normozoospermic and asthenozoospermic men.”, Systems biology in reproductive medicine, vol. 65 (6) , pp. 409–419, 2019.
    • M. Xavier, B. Nixon, S. Roman, R. Scott, J. Drevet and R. Aitken, “Paternal impacts on development: identification of genomic regions vulnerable to oxidative DNA damage in human spermatozoa.”, Hum. Reprod., 2019.
    • C. Chu, Y. Zhang, L. Yu, S. Sharma, Z. Fei and J. Drevet, “Epididymal small non-coding RNA studies: progress over the past decade.”, Andrology, vol. 7 (5) , pp. 681–689, 2019.
    • R. Guiton, A. Voisin, J. Henry-Berger, F. Saez and J. Drevet, “Of vessels and cells: the spatial organization of the epididymal immune system.”, Andrology, vol. 7 (5) , pp. 712–718, 2019.
    • F. Saez, M. Whitfield and J. Drevet, “Impairment of sperm maturation and capacitation due to diet-dependent cholesterol overload.”, Andrology, vol. 7 (5) , pp. 654–661, 2019.
    • A. Voisin, F. Saez, J. Drevet and R. Guiton, “The epididymal immune balance: a key to preserving male fertility.”, Asian J. Androl., 2019.
    • R. J. Aitken, G. N. D. Iuliis and J. R. Drevet, “Role of Oxidative Stress in the Etiology of Male Infertility and the Potential Therapeutic Value of Antioxidants”, Oxidants, Antioxidants and Impact of the Oxidative Status in Male Reproduction, pp. 91–100, 2019.
    • J. Drevet and R. Aitken, “Oxidative Damage to Sperm DNA: Attack and Defense.”, Advances in experimental medicine and biology, vol. 1166 , pp. 107–117, 2019.
    • J. Pariz, C. Ranea, R. Monteiro, D. Evenson, J. Drevet and J. Hallak, “Melatonin and Caffeine Supplementation Used, Respectively, as Protective and Stimulating Agents in the Cryopreservation of Human Sperm Improves Survival, Viability, and Motility after Thawing compared to Traditional TEST-Yolk Buffer.”, Oxidative medicine and cellular longevity, vol. 2019 , pp. 6472945, 2019.
    • F. Saez and J. Drevet, “Dietary Cholesterol and Lipid Overload: Impact on Male Fertility.”, Oxidative medicine and cellular longevity, vol. 2019 , pp. 4521786, 2019.
  • 2018
    • A. Champroux, C. Damon-Soubeyrand, C. Goubely, S. Bravard, J. Henry-Berger, R. Guiton, F. Saez, J. Drevet and A. Kocer, “Nuclear Integrity but Not Topology of Mouse Sperm Chromosome is Affected by Oxidative DNA Damage.”, Genes, vol. 9 (10) , 2018.
    • E. El Khouri, M. Whitfield, L. Stouvenel, A. Kini, B. Riederer, P. Lores, D. Roemermann, G. di Stefano, J. Drevet, F. Saez, U. Seidler and A. Toure, “Slc26a3 deficiency is associated with epididymis dysplasia and impaired sperm fertilization potential in the mouse.”, Molecular reproduction and development, vol. 85 (8-9) , pp. 682–695, 2018.
    • N. Podechard, S. Ducheix, A. Polizzi, F. Lasserre, A. Montagner, V. Legagneux, E. Fouche, F. Saez, JM. Lobaccaro, L. Lakhal, S. Ellero-Simatos, P. Martin, N. Loiseau, J. Bertrand-Michel and H. Guillou, “Dual extraction of mRNA and lipids from a single biological sample.”, Scientific reports, vol. 8 (1) , pp. 7019, 2018.
    • S. Vorilhon, F. Brugnon, A. Kocer, S. Dollet, C. Bourgne, M. Berger, L. Janny, B. Pereira, R. Aitken, A. Moazamian, P. Gharagozloo, J. Drevet and H. Pons-Rejraji, “Accuracy of human sperm DNA oxidation quantification and threshold determination using an 8-OHdG immuno-detection assay.”, Hum. Reprod., vol. 33 (4) , pp. 553–562, 2018.
    • A. Voisin, M. Whitfield, C. Damon-Soubeyrand, C. Goubely, J. Henry-Berger, F. Saez, A. Kocer, J. Drevet and R. Guiton, “Comprehensive overview of murine epididymal mononuclear phagocytes and lymphocytes: Unexpected populations arise.”, Journal of reproductive immunology, vol. 126 , pp. 11–17, 2018.
    • A. Champroux, J. Cocquet, J. Henry-Berger, J. Drevet and A. Kocer, “A Decade of Exploring the Mammalian Sperm Epigenome: Paternal Epigenetic and Transgenerational Inheritance.”, Frontiers in cell and developmental biology, vol. 6 , pp. 50, 2018.
    • H. Levine, H. Mohri, A. Ekbom, L. Ramos, G. Parker, E. Roldan, L. Jovine, S. Koelle, A. Lindstrand, S. Immler, S. Mortimer, D. Mortimer, G. van der Horst, S. Ishijima, N. Aneck-Hahn, E. Baldi, R. Menkveld, S. Rothmann, A. Giwercman, Y. Giwercman, M. Holmberg, U. Kvist, L. Bjorndahl, R. Holmberg, S. Arver, J. Flanagan and J. Drevet, “Male reproductive health statement (XIIIth international symposium on Spermatology, may 9th-12th 2018, Stockholm, Sweden.”, Basic and clinical andrology, vol. 28 , pp. 13, 2018.
    • J. Drevet, “Epididymal approaches to male contraception.”, Basic and clinical andrology, vol. 28 , pp. 12, 2018.
  • 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.
    • 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. Drevet, “Sperm DNA integrity testing: a valuable addition to the tool box of infertility clinicians.”, Translational andrology and urology, vol. 6 (Suppl 4) , pp. S590–S591, 2017.
    • C. Moretti, M. Serrentino, C. Ialy-Radio, M. Delessard, T. Soboleva, F. Tores, M. Leduc, P. Nitschke, J. Drevet, D. Tremethick, D. Vaiman, A. Kocer and J. Cocquet, “SLY regulates genes involved in chromatin remodeling and interacts with TBL1XR1 during sperm differentiation.”, Cell death and differentiation, vol. 24 (6) , pp. 1029–1044, 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.
    • J. Carreira, J. Trevizan, I. Carvalho, B. Kipper, L. Rodrigues, C. Silva, S. Perri, J. Drevet and M. 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 , pp. 12, 2017.
  • 2016
  • 2015
  • 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.
    • A. Noblanc, A. Kocer and J. Drevet, “Recent knowledge concerning mammalian sperm chromatin organization and its potential weaknesses when facing oxidative challenge.”, Basic and clinical andrology, vol. 24 , pp. 6, 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.
    • H. Pons-Rejraji, C. Artonne, B. Sion, F. Brugnon, M. Canis, L. Janny and G. Grizard, “Prostasomes: inhibitors of capacitation and modulators of cellular signalling in human sperm.”, Int. J. Androl., vol. 34 (6 Pt 1) , pp. 568–80, 2010.
    • F. Brugnon, L. Janny, Y. Communal, C. Darcha, C. Szczepaniak, F. Pellestor, P. Vago, H. Pons-Rejraji, C. Artonne and G. Grizard, “Apoptosis and meiotic segregation in ejaculated sperm from Robertsonian translocation carrier patients.”, Hum. Reprod., vol. 25 (7) , pp. 1631–42, 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.
    • G. Remerand, E. Merlin, R. Froissart, F. Brugnon, J. Kanold, L. Janny and F. Demeocq, “Four successful pregnancies in a patient with mucopolysaccharidosis type I treated by allogeneic bone marrow transplantation.”, J. Inherit. Metab. Dis., vol. 32 Suppl 1 , pp. S111–3, 2009.
    • H. Pons-Rejraji, J. Bailey and P. Leclerc, “Modulation of bovine sperm signalling pathways: correlation between intracellular parameters and sperm capacitation and acrosome exocytosis.”, Reprod. Fertil. Dev., vol. 21 (4) , pp. 511–24, 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
    • C. Patrat, T. Bienvenu, L. Janny, A. Faure, P. Fauque, I. Aknin-Seifer, C. Davy, N. Thiounn, P. Jouannet and R. Levy, “Clinical data and parenthood of 63 infertile and Y-microdeleted men.”, Fertil. Steril., vol. 93 (3) , pp. 822–32, 2008.
    • F. Brugnon, F. Bilan, M. Heraud, G. Grizard, L. Janny and I. Creveaux, “Outcome of intracytoplasmic sperm injection for a couple in which the man is carrier of CFTR p.[R74W;V201M;D1270N] and p.P841R mutations and his spouse a heterozygous carrier of p.F508del mutation of the cystic fibrosis transmembrane conductance regulator gene.”, Fertil. Steril., vol. 90 (5) , pp. 2004.e23–6, 2008.
    • F. Brugnon, L. Janny, C. Artonne, B. Sion, J. Pouly and G. Grizard, “Activated caspases in thawed epididymal and testicular spermatozoa of patients with congenital bilateral absence of the vas deferens and intracytoplasmic sperm injection outcome.”, Fertil. Steril., vol. 92 (2) , pp. 557–64, 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.
    • 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.