VIRAL AND CHEMICAL ENVIRONMENT & REPRODUCTION
Viruses & Reproduction (contact Nathalie Dejucq-Rainsford)
Viral infections of the male genital tract have been little studied yet they can have several dramatic consequences such as the spread of viruses via semen, the formation of drug-resistant sanctuaries, the induction of infertility, and the development of cancers affecting male sexual organs. Our work aims at a better understanding of the interactions between viruses and the male genital tract, with emphasis on HIV.
Our research focusses on:
- Deciphering the origin of HIV in semen. Semen is the main vector of HIV dissemination worldwide but the origin of the infected cells and viral particles contaminating this body fluid is still unclear. To identify the productive sources of HIV in semen, we study HIV/SIV target organs and cells in the male genital tract in human and animal models.
- Determining whether the male genital tract constitutes a sanctuary for HIV. In a subset of men whose blood viral load is undetectable under prolonged antiretroviral therapy, infectious HIV persists in semen. To identify the HIV reservoirs in the seminal tract, we study the impact of current antiretroviral therapies on HIV/SIV infection of genital organs and semen.
- Exploring the modulating effect of semen on HIV sexual transmission. Semen is a complex fluid encompassing over 1100 proteins and displaying antimicrobial and immunomodulatory activities. Semen soluble factors are likely to interfere with the sexual transmission of HIV. The objective of our research is to identify seminal proteins that impact on HIV infectivity to help the design of therapy to decrease the sexual transmission of HIV.
- Analysing the testicular antiviral response and its consequences on reproductive functions. We have analyzed the anti-viral defense capacity of the testis and showed that the rodent testis can produce high concentrations of interferons and antiviral proteins in response to a viral infection. We are currently studying the impact of the testis innate immune response on fertility.
The research projects carried out by the team are based on in vivo and in vitro approaches in humans and animals and on a wide variety of cellular and molecular biological methods including large scale screening techniques (proteomics/ transcriptomics). Our work is supported by funding from ANRS, Inserm, Sidaction, Ministère de l’enseignement supérieur et de la recherche and Région Bretagne.
Toxics & Reproduction (contact Bernard Jégou)
Infertility is a serious medical problem in industrialized countries. Very little is know about the causes of this phenomenon and no curative therapy is currently available. 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 pathologies and an increase in the frequency of cancer. To better understand the molecular causes of human male reproductive failure we employ toxicological and genome- as well as molecular biological approaches.
Our research focusses on:
- Analysing direct effects of phtalates (considered to be EDs because of their anti-androgenic activities) on the development of ex vivo rat fetal testes cultures (Fetal Gonad Assay – FEGA) and human testes. Samples are analysed by qualitative and quantitative histology, by monitoring testicular biomarkers and by genome biological approaches.
- 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.
- Proteome profiling of efferent ducts connecting testes and epididymis. They absorb 90% of the testicular fluid in a testosterone and oestradial-dependent manner and might therefore be affected by EDs. With the fluid the ducts also absorb most of the proteins in it and therefore we hope to identify biomarkers of hormone and ED action.
- Development and phenotypic analysis of mouse models for reproductive pathologies linked to individual loci by gene over-expression or deletion.