Axis 3 | Genetics, toxicology and diagnostics in human male reproduction

  1. Roles of the epididymis in post testicular sperm maturation
  2. The impact of small molecules on the male reproductive sphere
  3. Development of a predictive assay to assess the presence of germ cells and their stage of maturation in the testes of infertile men
Reproduction

Roles of the epididymis in post testicular sperm maturation

Principal Investigators: Charles Pineau, Emmanuelle Com and Mélanie Lagarrigue

We have established extensive proteomes of testicular cells, sperm cells and seminal plasma. Based on these previous results, we now study (i) the role played by different regions of the epididymis in sperm maturation during the transit of the male gamete through the organ; (ii) the dynamics of exchanges between the endothelium epididymis, seminal plasma and sperm, and (iii) map by 3D reconstruction metabolites and protein distribution along the organ. Finally, (iv) we aim at correlating the maturation defect of one or more proteins of interest with a subfertility or infertility phenotype, such as impaired mobility or sperm-oocyte interaction defects in the mouse and/or human.

Relevant publications: PubMed

The impact of small molecules on the male reproductive sphere

Principal Investigators: Charles Pineau and Mélanie Lagarrigue

Our work focusses on molecules, which are environmentally, economically or clinically relevant. We study the tissular and cellular distribution of environmental or therapeutical toxicants such as Chlordecone, Bisphenol A and 5-FU, to better understand their cytotoxic effect on male germ cells, and to identify in situ their cellular partners and metabolites. This work will help assess the impact of environmental and therapeutic compounds on human reproductive health using cutting-edge technologies in the field of MALDI mass spectrometry imaging.

Relevant publications : PubMed

Development of a predictive assay to assess the presence of germ cells and their stage of maturation in the testes of infertile men

Principal Investigators: Charles Pineau and Nathalie Melaine

To date, there is no powerful predictor of the probability to recover living sperm cells in non-obstructive azoospermic (NOA) men. Using an integrative proteomics strategy, we have identified 92 specific protein markers of post-meiotic germ cells whose presence/absence could be monitored in seminal plasma in order to select only non-obstructive azoospermia patients whose testes likely contain spermatozoa. We pursue the development of a multiplex ELISA assay which major objective is to evaluate the informative power of each marker assay for predicting the presence of mature germ cells in the testes of NOA patients and thus to predict the outcome of testicular biopsies. A blind retrospective validation involving several ART centers will be conducted. Our multiplex assay - named Fertichip - should be a valuable diagnostic tool for clinicians in the field of male infertility.

Relevant publications: PubMed

Patent: US Patent 9,188,582 B2 (17 nov 2015). Methods for predicting the presence of reproductive cells in the testis. Pineau C, Rolland AD, Calvel P, Lavigne R.