COCAINE ALTERS MOUSE GERM CELLS EPIGENOME WITH DIRECT IMPACT ON H4ac EXPRESSION AND DNA METHYLATION IN THE SPERM

GAMBINI PANTOJA CAMILO R; CANDELA R. GONZALEZ; BETINA GONZALEZ; BISAGNO, VERONICA; ALFREDO VITULLO

Mar del Plata

Congreso; SAIC - SAI - SAFIS 2018; 2018

Cocaine intake is associated with testicular toxicity and significantreproductive function impairment. There is accumulating evidencethat cocaine administration can trigger nongenetic inheritancethrough the male germ line affecting development and behavior ofthe offspring. The influence of environmental factors on the epigenomeof male germ cells appears to be most impactful if it happensduring a developmental phase when these cells are epigeneticallyreprogrammed. In the present study, we measured epigenetic marksin isolated germ cells of adult mice treated with cocaine (10 mg/kg) or vehicle, in an intermittent binge protocol (3 i.p. injections, 1h apart, one day on/off for 13 days). We found that chronic cocaineintake disrupts male germ cell epigenetic homeostasis, increasingglobal methylated citocine (5-mC) levels in DNA from germ cells andcauda epididymal sperm (germ cells: vehicle 13.15 ± 0.99 vs cocaine20.113 ± 2.28; sperm: vehicle 15.81 ± 1.08 vs cocaine 21.35± 1.52). Cocaine also increased acetylated histone 4 (H4ac) proteinlevels and decreased class I deacetylases HDAC1/2 mRNA andprotein expression (p