Keywords : physiology, reproduction, ecophysiology, male function, fertility, endocrine disruptor, testis, parasitoid, mechanism of action
Research project :
In recent years, the observation of a rapid decline in male reproductive quality is becoming a major societal concern. On top of affecting public health, as Humans appeared to be also affected, it can have negative consequences on the world food production by reducing the reproductive capacities of species of agronomic importance, such as pollinators and biological control agents. Causes are multifactorial and they most likely involve environmental changes such as the increasing exposure of animals to anthropogenic chemicals and thermal stresses associated with global warming. Although invertebrates constitute the vast majority of the animal kingdom, little effort has been made to evaluate the environmental consequences of chemicals inducing endocrine disruption or temperature global change on their reproductive abilities. Similarly, mechanisms responsible for the decrease in spermatogenesis are not wholly elucidated. In parasitic wasps, different biotic and abiotic factors applied during male development have the same consequences: reduced sperm stock and decreased fitness. In haplo-diploid species as parasitoids, the female ability to produce daughters depends on the availability of sperm stored in the spermatheca after mating and successful insemination. Therefore, parasitic wasps appear to be excellent candidates for analyzing the effects of environmental stresses on male functions. They are natural enemies of a broad range of arthropods of medical, veterinary and agricultural significance. More particularly, Nasonia vitripennis wasp presents several advantages: first, the complete genome sequence and the RNAi tools are available. Second, due to the rapid development of this organism, the consequences of different environmental perturbations on fertility, reproductive success and F1 population dynamics are easy, cheap and fast to measure. The main objective of this project is therefore to determine the mechanisms responsible for the observed decrease in fertility of N. vitripennis males when submitted to a chemical and a thermal stress, presented either separately or in combination. As a chemical stress, we propose to investigate the effect of di(2-ethylhexyl) phthalate (DEHP) and ecdysteroids. As a thermal stress, we will expose the individuals to sub-lethal heat stress. Additionally, an ecotoxicogenomic approach at the transcriptomic level will allow us to characterize the gene expression variations associated to these perturbations and identify the genes pathway controlling male functions. The function of candidate genes will then be studied under these environmental perturbations. Our long-term ambition is therefore to propose N. vitripennis as lab-sentinels of potential effects on hymenopterans and a comparative model for the study of spermatogenesis regulation in mammals.
N’Tumba-Byn T, Moison D, Lacroix M, Lécureuil C, Lesage L, Prud’homme S, Pozzi-Gaudin S, Frydman R, Benachi A, Livera G, Rouiller-Fabre* V, Habert* R. 2012 Differential Effects of bisphenol A and diethylstilbestrol on human, rat and mouse fetal Leydig cell function, Plos One, 7(12):e48266 *These authors contributed equally to this work
Muczynski V, Lécureuil C, Messiaen S, Guerquin MJ, N’tumba-Byn T, Moison D, Hodroj W, Benjelloun H, Baijer J, Livera G, Frydman R, Benachi A, Habert R, Rouiller-Fabre V. 2012 Cellular and molecular effect of MEHP involving LXRα in human fetal testis and ovary. Plos One, 7(10):e48266
Suire, S., Lécureuil, C., Anderson, K., Damoulakis, G., Niewczas, I., Davidson, K., Guillou, H., Pan, I., Wu, D., Clark, J., Hawkins*, P., Stephens*, L. 2012 GPCR activation of Ras and PI3Kg in neutrophils depends on PLCb2/b3 and the RasGEF RasGRP4. EMBO Journal, 31:3118-3129 *These authors contributed equally to this work
Tartarin*, P., Moison*, D., Guibert, E., Dupont, J., Habert, R., Rouiller-Fabre, V., Frydman, N., Pozzi, S., Frydman, R., Lécureuil*, C, Froment*, P. 2012 Possible consequences of metformin treatment on testis development in human and murine foetus. Human reproduction, 27:3304-3314 *These authors contributed equally to this work
Lambrot, R.*, Muczynski, V.*, Lécureuil, C., Angenard, G., Coffigny, H., Pairault, C., Moison, D., Frydman, R., Habert, R. & Rouiller-Fabre, V. 2009 Phthalates impair germ cell development in the human fetal testis in vitro without change in testosterone production. Environ Health Perspect 117, 32-7. *These authors contributed equally to this work
Lécureuil, C., Staub, C., Fouchecourt, S., Maurel, M. C., Fontaine, I., Martinat, N., Gauthier, C., Daudignon, A., Delaleu, B., Sow, A., Jegou, B. & Guillou, F. 2007 Transferrin overexpression alters testicular function in aged mice. Mol Reprod Dev 74, 197-206.
Guillou, H., Lécureuil, C., Anderson, K. E., Suire, S., Ferguson, G. J., Ellson, C. D., Gray, A., Divecha, N., Hawkins, P. T. & Stephens, L. R. 2007 Use of the GRP1 PH domain as a tool to measure the relative levels of PtdIns(3,4,5)P3 through a protein-lipid overlay approach. J Lipid Res 48, 726-32.
Lécureuil, C., Tesseraud, S., Kara, E., Martinat, N., Sow, A., Fontaine, I., Gauthier, C., Reiter, E., Guillou, F. & Crepieux, P. 2005 Follicle-stimulating hormone activates p70 ribosomal protein S6 kinase by protein kinase A-mediated dephosphorylation of Thr 421/Ser 424 in primary Sertoli cells. Mol Endocrinol 19, 1812-20.
Lécureuil, C., Saleh, M. C., Fontaine, I., Baron, B., Zakin, M. M. & Guillou, F. 2004 Transgenic mice as a model to study the regulation of human transferrin expression in Sertoli cells. Hum Reprod 19, 1300-7.
Lécureuil, C., Fontaine, I., Crepieux, P. & Guillou, F. 2002 Sertoli and granulosa cell-specific Cre recombinase activity in transgenic mice. Genesis 33, 114-8.