Stage proposé par « Bernard JÉGOU » Nom et adresse du Laboratoire ou de l’Unité :
Université de Rennes 1 - Campus de Beaulieu
Téléphone : 02.23.23.69.11. Mail : bernard.jégou@inserm.fr Site internet : http://www.irset.org/ Directeur du Laboratoire ou de l’Unité : Bernard JÉGOU Intitulé de l ‘équipe d’accueil : Virus, Environnement Chimique & Reproduction
Prénom et NOM du Responsable de l’équipe : Nathalie DEJUCQ-RAINSFORD Résumé du thème de recherche de l’équipe : Endocrine disruptors (EDs) cause various pathologies because they interfere with hormone synthesis, secretion, transport, action and metabolism. This phenomenon can affect the exposed individual and/or his offspring. EDs are possibly implicated in a number of reproductive abnormalities and an increase in the frequency of cancer. To better understand the environmental-induced human male reproductive and development failures, we employ toxicological and genome- as well as molecular biological approaches. Our research focusses on:
1. Analysing direct effects of potential EDs on the development of ex vivo rat fetal testes cultures and
human testes. Samples are analysed by qualitative and quantitative histology, by monitoring testicular biomarkers and by genomic biological approaches.
2. Generation of a comprehensive expression map of mammalian testis. To this end we study highly
enriched testicular somatic and germ cells and compare them to whole-gonad controls in the rat and in rodents and human. Moreover, we study the expression program of Sertoli cells from pre-pubertal to adult stages using the rat as a model system. Microaray expression data are integrated with proteome analysis of testicular cells.
3. Development and phenotypic analysis of mouse models for reproductive pathologies linked to individual
loci by gene over-expression or deletion.
Titre du projet de stage : Individual and combined effects of anti-androgenic endocrine disruptors in the human testis
Prénom, NOM, téléphone et adresse e-mail du responsable du stage: Bernard JÉGOU IRSET INSERM U1085 Université de Rennes 1 – Campus de Beaulieu 35042 RENNES CEDEX bernard.jegou@inserm.fr Projet de stage : After decades of very useful researches on a chemical-by-chemical basis, agencies have begun to consider cumulative risk of chemicals. This results from the fact that humans are exposed to multiples chemicals and agents of different origins. In recent years, it has become clear that, although essential for screening approaches and mechanistic studies on EDs, continuation of a focus on single chemicals is likely to underestimate risks that arise from exposure to several chemicals simultaneously, and this has motivated calls for taking account of mixture effects in risk assessment and epidemiology. However, efforts of defining real world conditions that lead to real world exposures to combinations of chemicals relevant to humans are in their infancy. With doubts cast on the relevance of the rat as a model for human effects, work with the human testis has assumed high relevance. More than 8% of all chemicals have been identified as anti-androgens, including certain phthalates, widely used as plasticizers, pesticides and various other chemicals found in food and consumer products. This is of concern because steroidal androgens are key regulators of male sexual differentiation and that disruption of androgen action may lead to a ‘testicular dysgenesis syndrome’ (TDS).
The project aims at assessing the effects of individual and/or combined mixed anti-androgenic chemicals in the human testis. Techniques mises en œuvre par le stagiaire : Organotypic culture, cell biology, molecular biology, toxicology, immunoassays, immunohistochemistry, transcriptomics. Publications du Responsable de stage au cours des 5 dernières années :
→ Kristensen DM, Lesné L, Le Fol V, Desdoits-Lethimonier C, Dejucq-Rainsford N, Leffers H, Jégou B. Paracetamol (acetaminophen), aspirin (acetylsalicylic acid) and indomethacin are antiandrogenic in rat foetal testis. Int J Androl. 2012 (sous presse)
→ Desdoits-Lethimonier C*, Albert O*, Le Bizec B, Perdu E, Zalko D, Courant F, Lesné L, Guillé F, Dejucq-
Rainsford N, Jégou B.Human steroidogenesis is inhibited by phthalates. Hum Reprod. 2012 May;27(5):1451-9
→ Kristensen DM, Hass U, Lesné L, Lottrup G, Jacobsen PR, Desdoits-Lethimonier C, Boberg J, Petersen
JH, Toppari J, Jensen TK, Brunak S, Skakkebaek NE, Nellemann C, Main KM, Jégou B, Leffers H. Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat. Hum Reprod. 2011 Jan;26(1):235-44
→ Kristensen DM, Skalkam ML, Audouze K, Lesné L, Desdoits-Lethimonier C, Frederiksen H, Brunak
S, Skakkebæk NE, Jégou B, Hansen JB, Junker S, Leffers H. Many putative endocrine disruptors inhibit prostaglandin synthesis. Environ Health Perspect. 2011 Apr;119(4):534-41. Apr;119(4):534-41.
→ Chauvigné F, Plummer S, Lesné L, Cravedi JP, Dejucq-Rainsford N, Fostier A, Jégou B.Mono-(2- ethylhexyl) phthalate directly alters the expression of Leydig cell genes and CYP17 lyase activity in cultured rat fetal testis. PLoS One. 2011;6(11):e27172.
→ Chauvigné F, Menuet A, Lesné L, Chagnon MC, Chevrier C, Regnier JF, Angerer J, Jégou B.Time- and dose-related effects of di-(2-ethylhexyl) phthalate and its main metabolites on the function of the rat fetal testis in vitro. Environ Health Perspect. 2009 Apr;117(4):515-21.
Autres informations: Etudiants actuellement en thèse ou en M2 dans l’équipe d’accueil.
• Océane ALBERT (PhD student – 3rd year)
• Céline CAMUS (PhD student – 2nd year)
• Clémentine CHALMEY (PhD student - 2nd
• Claire DELEAGE (PhD student – 4th year)
• Marina MOREAU (PhD student – 4th year)
Etudiants ayant préparé ou soutenu leur thèse ou leur M2 dans l’équipe d’accueil au cours des six dernières années. Pour chaque étudiant indiquez le nom du responsable de l’étudiant, l’année du début de la thèse et de fin de la thèse, l’Ecole Doctorale de rattachement et le devenir de l’étudiant. Responsable Année de début Soutenance Ecole doctorale ROULET Vanessa TREPOS Mélanie LE TORTOREC Anna
Cette proposition de stage s’adresse-t-elle spécifiquement à un étudiant scientifique, médecin ou vétérinaire ou bien est-il ouvert à tous les profils ? Profil ouvert Ce sujet peut-il donner lieu à une thèse ? Oui
Enzyme Immunoassay (EIA) Kits □ Thyroid □ TORCH and Infectious Diseases □ Fertility □ Steroids □ Tumor Markers □ Other Analytes □ Cardiac Markers Tiroiduli funqcia / THYROID Intended Use: For the in vitro quantitative determination of the thyroid stimulating hormone (TSH) concentration in human serum. Minimum Sensitivity: 0.2 µIU/ml FDA Cleared, CE Cleared
New York State Department of Health AIDS Institute D. Counsel/treat the healthcare worker. • Offer PEP as soon as possible following exposure, ideally within 2 hours • Discuss significance of exposure; provide scientifically accurate and not more than 36 hours after exposure. information about the known risks of seroconversion and transmission. • If the survivor is too di