5-AZA-2'-deoxycytidine (5-AZA-CdR): a demethylating agent affecting development and reproductive capacity.
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 significantly lower (P < 0.01) than the controls except for the number of spermatid heads per milligram of testis.
Cisneros
F Javier
FJ
Department of Anatomy, Physiological Sciences and Radiology, College of Veterinary Medicine, North Carolina State University, NC 27695, USA.
Branch
Stacy
S
D000704:Analysis of Variance; D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000633:toxicity*; D001824:Body Constitution / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D000077209:Decitabine; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D005260:Female; D005836:Genitalia, Female / Q000187:drug effects; D008297:Male; D051379:Mice; D011247:Pregnancy / Q000187:drug effects; D012098:Reproduction / Q000187:drug effects*; D013087:Spermatids / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000097:blood
D013739:Testosterone; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine