Paris Postdoc Seminar – Alberto De La Iglesia

Invité par l’Institut Jacques Monod, Alberto de la Iglesia, Ph.D. Institut Cochin (Inserm U1016 – CNRS UMR8104 – Université Paris Cité) Dr. Julie Cocquet Group « Epigenetics & Spermatogenesis », part of the VAIMAN Team “From Gametes to Birth: Genomics, Epigenetics, and Physiopathology of Reproduction” présentera un Paris Postdoc Seminar sur le thème :

Exploring the role of metabolism-dependent histone acylations during male germ cell differentiation and their sensitivity to metabolic perturbations 

Résumé :

The paternal epigenome is established during spermatogenesis and is particularly responsive to environmental cues. In line with the POHaD paradigm (Paternal Origins of Health and Disease), increasing evidence shows that environmentally induced paternal epigenetic alterations can have effects beyond fertilization, which is the case of paternal obesity. Within this context, our lab is interested in a type of epigenetic marks named histone acylations, whose abundance depends upon the availability of their precursor metabolites and, hence, are sensitive to the cell metabolic status. Among the different histone acylations, we have recently characterized that lactylation modifies several histone lysine residues in wild-type mouse testis by proteomics approaches (Manessier et al., 2026; PMID 42285509).

To better understand the effects of a metabolic stress on coordinated metabolo-epigenetic signatures in male germ cells, we established a mouse model of Western style diet-induced obesity (WD; high-fat/high-sugar, 16 weeks). WD males exhibit an altered testicular metabolome, characterized by changes in pathways related to energy metabolism and the generation of precursors of epigenetic marks. In parallel, we identified altered histone acylation levels in male germ cells of WD mice, suggesting a link between the observed metabolomic and epigenetic alterations. Multi-omics approaches in WD mice are currently being analyzed to determine the sensitivity to metabolic changes in male germ cells.

Thus, our work supports that the testis can sense metabolic disturbances, leading to dysregulations in developing male germ cells at the metabolic and epigenetic levels. These alterations could contribute to the effects of male obesity beyond fertilization described in the POHaD framework.