Notre équipe présente cette année un sujet de thèse auprès de l’école doctorale de Clermont-Ferrand. Le concours pour obtenir un contrat doctoral de 3 ans aura lieu début Juillet 2022.

Notre sujet porte sur les atteintes des cellules germinales souches (Spermatogonial Stem Cells ; SSC) qui sont associées à des passages inter- ou transgénérationnels d’anomalies à la descendance à la suite d’expositions à des composés exogènes.  Pour cela nous utilisons des modèles murins expérimentaux (modulations géniques, transplantation de cellules souches,…) , des modèles cellulaires ainsi que le nématode C. elegans.

Le but étant de comprendre comment des modulations transitoires de l’homéostasie de ces SSC peuvent être associées à des effets à long terme notamment sur plusieurs générations et de définir les mécanismes moléculaires impliqués.

Les candidats doivent être en master-2 cette année ou être titulaire d’un diplôme de M2.

 De plus, l ’école doctorale de Clermont-Ferrand demande un classement dans la 1^ère partie de votre M2.Pour de plus amples informations n’hésitez pas à me contacter (david.volle@uca.fr).

Our team was created in January 2017. Our thematic is mainly focused on the links between altered bile acid metabolism, environmental exposures and testicular pathophysiologies leading to male fertility disorders with a focus on spermatogonial stem cell niche biology. This allows us to put forward new hypothesis and innovative research strategies on spermatogenesis, fertility disorders, testicular germ cell cancer and transgenerational inheritance of diseases.

Context.  Male fertility disorders have been correlated with adverse conditions such as exposure to environmental molecules (EM, including endocrine disrupters or anti-cancer drugs) or metabolic disorders. Indeed, epidemiological studies have highlighted an unexpected link between liver diseases (LD) and male fertility disorders. The incidence of metabolic diseases has increased over the last decades, and it is estimated that 29 millions of Europeans face chronic LDs. These findings urge the need to better clarify the links between LDs and male fertility disorders. Interestingly, bile acid (BA) concentrations are increased in almost all LDs. We thus wanted to decipher the consequences of BA exposures on male fertility with a focus on the establishment of the spermatogonial stem cell niche and the maintenance of the spermatogonial stem cells (SSCs) pool, which is established during fetal and neonatal life regarding species. Of interest, the alterations of SSC could lead to long-term or irreversible effects through quantitative and/or qualitative alterations of germ cell lineage.

Objectives. Our aim is to elucidate the cellular and molecular mechanisms that support the harmful effects of BAs and EMs with an impact on male reproductive functions. This is a main issue to tackle since it would contribute to understand how changes in the local SSC niche environment due to EM exposures and/or altered BA metabolism could affect SSC biology and identity - to promote pathologies such as infertility, testicular germ cell tumors (TGCT), or alter germ cell quality associated with paternal transgenerational transmission of diseases. Regarding the BA signaling pathways we do analyze the involvement of the known BA receptors such as FXRa, TGR5, PXR and CAR.

Models and approaches. We will achieve these goals using a combination of high-throughput technologies (RNAseq, ChIP-seq, metabolomic) to investigate differential metabolic pathways and gene expression profiles from model cell lines, genetically modified animals (mouse, nematode) and human clinical samples. This should be facilitated by our free access to GReD’s plateform including animal house facilities and phenotyping (Anipath), FACs cell sorting with single cell analysis technologies, cell culture and imaging as well as bio-informatics devices that will secure our high throughput analysis.

Based on our achievements, we have defined clear objectives for the new contract, which are to:

1/ analyze the connections between the liver-intestine axis and testis with an impact on male fertility disorders;

 2/ study the roles of BA signaling pathways in TGCT etiology and sensitivity to anticancer therapies;

3/ characterize the BA-induced mechanisms associated with transgenerational transmission of diseases.

Expected results. This innovative project represents a research area, which has not been explored so far, allowing us to proposed new perspectives on the roles of BA and EMs on male fertility, testicular pathophysiology (infertility or cancer) and paternal inheritance. The purpose of the project aims to gain knowledge in these fields of research and in turn to propose markers for diagnosis or prognostics of reproductive diseases or inherited metabolic disorders. A final goal will be toinform sanitary agencies and people for prevention and precaution regarding the links between liver diseases, EM exposures and reproductive disorders and/or transmission of diseases to their progeny.

We are ready to study propositions to make demands for post-doc or PhD students.

We will also study carefully the demands of motivated young researchers who wish to join our group either by presenting to the recruitment competitions or by changing assignments.

 See what we are doing in our lab:

https://www.youtube.com/watch?v=ESKd-_U6420