Embryonic exposure to 5‐AZA‐2’‐Deoxycytidine (5‐AZA‐CdR) can affect epididymal sperm numbers of adult CD‐1 mice ‐ Epigenetic Implications

Abstract

Spermatogenesis and spermiogenesis demand adequate expression of specific genes at particular times. DNA methylation controls in part gene expression of mammals from embryogenesis to senescence. Altered epigenetic processes affecting sperm have been reported recently. The adverse effects of 5‐AZA‐CdR in sperm of adult mammals have been substantiated. Yet, its effects on sperm after an in utero insult remain to be elucidated. To investigate if an in utero exposure to 5‐AZA‐CdR – a demethylating agent‐ affects epididymal sperm numbers during adulthood. CD‐1 mice at gestation day 10 were administered 1 mg/kg of 5‐AZA‐CdR via intra peritoneal injection once. Body Weight, testis and epididimides of offspring were collected at post natal day 154. The number of epididymal sperm was determined by Computer Assisted Semen Analysis. Body Weight and epididymal sperm number of exposed mice were statistically lower than controls (P<0.05 and P<0.019 respectively) while relative testis and epididymis weights were not. This suggests that the 5‐AZA‐CdR in utero insult impaired spermatogenesis and/or spermiogenesis reducing the number of sperm present in the epididimides. Further studies are needed to elucidate the effects of altered methylation patterns induced during embryogenesis on sperm viability and/or availability during adulthood and the subsequent impact in the offspring of in utero exposed individuals. NIH‐ES08452 & CRL