PATERNAL EPIGENETIC PROGRAMMING: COCAINE TRIGGERS HISTONES POST-TRANSLATIONAL MODIFICATIONS IN MOUSE GERM CELLS

BISAGNO VERÓNICA; EDUARDO ROLDÁN; CANDELA R. GONZALEZ; BETINA GONZALEZ; ALFREDO VITULLO

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

Recent evidence indicates that paternal cocaine (coc) intake affects development and behavior of the offspring via epigenetic modifications. However, the mechanism by which coc alters germ cells epigenome has been poorly investigated. We previously showed that coc administration increases tyrosine hydroxilase expression and downregulates dopamine receptors DRD1 and DRD2 (doi:10.1371/journal.pone.0142713). Moreover, coc increased global 5-mC levels in DNA from germ cells and sperm, increased acetylated histone 4 (H4ac) and decreased class I deacetylases HDAC1/2 protein levels in germ cells (doi:10.1016/j.rbmo.2018.05.014). Here, we analyzed specific post-translational modifications (PTM) of histones in isolated germ cells of adult male mice treated with coc (10mg/kg) or vehicle (veh), in an intermittent binge protocol (3 i.p. injections, 1 h apart, one day on/off for 13 days). To evaluate the involvement of DRD1 in the deleterious action of coc, DRD1 antagonist SCH23390 (SCH, 0.05mg/kg) was injected 15 min before each coc or veh injection. Immunohistochemestry showed that H3K9ac, H3K27ac, H3K4me3 and H3K9me3 were localized in spermatogonia and early meiotic stages of spermatogenesis in veh and coc treated-mice. Coc increased H3K9ac and H3K9me3 and decreased H3K4me3 and H3K27ac protein levels in germ cells (p