Our research axes

Principal Investigator: Marjorie Whitfield, CRCN Inserm

Cilia are evolutionary conserved organelles that extend as single or multiple entities at the surface of nearly all cell types of the body. In humans, their structural and/or functional defects are associated with a growing number of inherited disorders, called ciliopathies. Their amazing characteristic is the manifestation of a broad range of symptoms going from chronic respiratory infections to cystic kidneys, obesity, diabetes, retinal degeneration, mental retardation and infertility. Although cilia share a core microtubule-based architecture, stunning variations of their organization exist between organisms or cell types. Their diversity is emphasized in mammals when comparing the flagellum of sperm cells to that of primary cilia found on many cell types. In this context, our laboratory initially investigated the role of the annulus, a peculiar ring-shaped structure surrounding the axoneme, which migrates during flagella assembly and which function remains virtually undefined. Our lab has recently provided novel information regarding the annulus and established several in vivo mouse models to investigate its function. Based on those recent findings, our current work combines cell biology, biochemistry, proteomics and mouse genetics with the aim of deciphering the precise functions and molecular mechanisms of the annulus in sperm flagella assembly.

Principal Investigators: Violaine Simon, MCF & Aminata Touré, DR CNRS

In mammals, sperm cells produced within the testis are structurally differentiated but remain immotile and are unable to fertilize the oocyte unless they undergo a series of maturation events during their transit through the male and female genital tracts. This post-testicular functional maturation is tightly controlled by the ion content, pH, and nutrient availability. In particular, ion fluxes play an essential role in controlling sperm motility and capacitation within the female genital tract. Our group was pioneer in investigating the functions of SLC26 transmembrane anion exchangers in sperm cells and showed their importance for activation of the cAMP-PKA pathway in cooperation with the CFTR channel. Overall, our work indicates that SLC26 channels constitute important regulators of anion fluxes in the processes of sperm maturation and activation. 

Our current work aims to characterize the signaling pathways involved in these processes, focusing on both ion channels and signaling proteins. We are also studying the signaling pathways of energy metabolism in spermatozoa.

Responsable de projet: Aminata Touré, DR CNRS

Asthenozoospermia, defined by the absence or reduction of sperm motility, is induced by structural defects of the sperm flagellum and/or functional alterations that impair flagellar beating and sperm progression. This condition is predominant as observed in nearly 80% of infertile men, but the genetic causes and associated pathophysiological mechanisms are still poorly defined. Our laboratory made major achievements in the genetic definition of human asthenozoospermia. In collaboration with physicians and geneticists, our group contributed to the identification of a dozen genes containing variants that account for asthenozoospermia due to severe morphological abnormalities of the flagellum (MMAF phenotype), in the context of isolated or syndromic, male infertility (i.e., Primary Ciliary Dyskinesia, ciliopathies). Importantly, our group also identified causes for human asthenozoospermia resulting from defects in sperm signaling pathways (SLC26A8, SLC9C1, IQCH). 

Our current work is focused on the functional characterization of novel genes identified with mutations in asthenozoospermic men. This work provides further knowledge on the molecular mechanisms required for proper sperm motility ; it also provide strong foundation for the development of both therapeutic and contraceptive strategies.