Transgenerational effects of prenatal ethanol ingestion-induced susceptibility to metabolic syndrome and the underlying mechanism in F2 rats / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To investigate the transgenerational effects of a hypothala mic-pituitary-ad-renal (HPA)axis -associated neuroendocrine metabolic progra mming alteration fro m F1 to adult second generation (F2)with prenatal ethanol ingestion.METHODS Pregnant Wistar rats were ad ministered with ethanol (4 mg·kg -1·d -1 )fro m gestational day 1 1 until delivery.F1 rats were fed a high-fat diet fro m postnatal week 4 (PW4)and were cross-mated in PW 16 -20.F2 rats were fed a standard diet fro m PW4 and rectal te mperature was measured in PW20,oral glucose tolerance test (OGTT)was con-ducted in PW21 ,blood sa mples and hypothala mus were collected in PW24 to investigate seru m lipids and HPA axis activity.RESULTS Co mparing to the F2 control group ,rectal te mperature in F2 ethanol group were higher (P<0.01 ),sugar tolerance in F2 male group was i mpaired (P<0.05),seru m corti-costerone and hypothala mus arginine vasopressin (AVP) mRNA were increased (P <0.05);seru m insulin were decreased (P<0.05)and male rats showed i mpaired glucose tolerance (P<0.05);seru m high-density lipoproteincholesterol (HDL-C)decrease (P <0.05)and total cholesterol (TCH)/HDL-C and low density lipoproteincholesterol (LDL-C)/HDL-C ratios were markedly increased (P <0.05,P <0.01 ).CONCLUSION Prenatal ethanol exposure induced metabolic syndro me has transgenerational effects,which may originate fro m the intrauterine progra mming of altered HPA axis-associated neuroen-docrine metabolis m.