Susceptibility to postnatal growth retardation induced by 5-AZA-2'-deoxycytidine in utero: gender specificity and correlation with reduced insulin-like growth factor 1.
The DNA demethylating agent 5-AZA-2'-deoxyxytidine (5-AZA-CdR) alters gene expression in mice exposed during developmental stages and causes malformations and growth suppression. The aim of this study was to determine if 5-AZA-CdR-induced growth retardation is associated with alterations in energy metabolism or in serum IGF-1 levels. Mice were exposed in utero to 5-AZA-CdR at gestation day 10. At postnatal day 21, exposed pups were weaned and body weights recorded. At 3 months of age, reproductive capacity was studied. At 5 months old, after body weight was recorded mice were killed and serum was collected to determine serum glucose, corticosterone, and IGF-1 levels. The body weights of both treated males and females were reduced at weaning compared with controls, but by 5 months of age, only the male body weight was affected. Reproductive capacity of males and females was reduced with males being more affected. Levels of corticosterone and glucose were not altered. Serum IGF-1 levels were lower in males exposed in utero to 5-AZA-CdR when compared to controls, but not in females, and correlated significantly with body weights. Our data suggest that the decreased levels of IGF-1 associated with the treatment could be the cause of the observed growth retardation in the in utero-exposed mice. A gender dimorphic effect, where males are more affected, is evident.
Cisneros
Francisco Javier
FJ
North Carolina State University, Environmental and Molecular Toxicology Department, 850 Main Campus Dr., Raleigh, NC 27695, USA.
Wilson
Ralph
R
Travlos
Gregory
G
Anderson
Lucy M
LM
Branch
Stacy
S
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000633:toxicity*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D000077209:Decitabine; D003864:Depression, Chemical; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006130:Growth Disorders / Q000139:chemically induced* / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D011247:Pregnancy; D012727:Sex Characteristics
D000964:Antimetabolites, Antineoplastic; D001786:Blood Glucose; D007334:Insulin-Like Growth Factor I; D000077209:Decitabine; D001374:Azacitidine; D003345:Corticosterone