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

GONZALEZ BETINA; GAMBINI PANTOJA CAMILO R; VITULLO ALFREDO DANIEL; BISAGNO VERÓNICA; GONZALEZ CANDELA ROCÍO

Reunión Conjunta de la Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Inmunología (SAI) y la Sociedad Argentina de Fisiología (SAFIS)

Congreso; LVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

SAIC-SAI-SAFE

Cocaine intake is associated with testicular toxicity and significant reproductive function impairment. There is accumulating evidence that cocaine administration can trigger nongenetic inheritance through the male germ line affecting development and behavior of the offspring. The influence of environmental factors on the epigenome of male germ cells appears to be most impactful if it happens during a developmental phase when these cells are epigenetically reprogrammed. In the present study, we measured epigenetic marks in isolated germ cells of adult mice treated with cocaine (10 mg/kg) or vehicle, in an intermittent binge protocol (3 i.p. injections, 1 h apart, one day on/off for 13 days). We found that chronic cocaine intake disrupts male germ cell epigenetic homeostasis, increasing global methylated citocine (5-mC) levels in DNA from germ cells and cauda epididymal sperm (germ cells: vehicle 13.15 ± 0.99 vs cocaine 20.113 ± 2.28; sperm: vehicle 15.81 ± 1.08 vs cocaine 21.35 ± 1.52). Cocaine also increased acetylated histone 4 (H4ac) protein levels and decreased class I deacetylases HDAC1/2 mRNA and protein expression (p