5‐AZA‐2′‐deoxycytidine (5‐AZA‐CdR): a demethylating agent affecting development and reproductive capacity

Abstract The objective was to evaluate the effects of 5‐AZA‐2′‐deoxycytidine (5‐AZA‐CdR) on postnatal development and reproductive capacity. Pregnant mice were administered 1 mg kg−1 5‐AZA‐CdR at gestation day 10. The body weights of F1 control and treated (in uterine‐exposed) pups were recorded. To evaluate the reproductive capacity, 5‐AZA‐CdR F1 males and females were mated with control mice. The presence of plugs and the number of pregnancies were recorded. The 5‐AZA‐CdR F1 male mice were killed. Total body, testes and epididymis weights were recorded. Spermatid head counting, histological analyses and serum testosterone levels were performed. Body weights of 5‐AZA‐CdR F1 mice were statistically lower than controls ( P  < 0.01), with the females more strongly affected ( P  < 0.05). Male mating capacity appeared to be more adversely affected. Mating of 5‐AZA‐CdR F1 males with control females resulted in a lower pregnancy rate compared with control mating groups ( P  < 0.01). Gross testicular and epididymis weights were lower in 5‐AZA‐CdR F1 mice ( P  < 0.01). However, testicular and epididymis weights in these mice were higher than controls when correlated to body weight ( P  < 0.01). In 5‐AZA‐CdR F1 male mice, all measured reproductive parameters, including total number of spermatid heads per testis, are signicantly lower ( P  < 0.01) than the controls except for the number of spermatid heads per milligram of testis. Published in 2003 by John Wiley & Sons, Ltd.