Transgenerational effects of fetal and neonatal exposure to nicotine.

A wide variety of in utero insults are associated with an increased incidence of metabolic disorders in the offspring and in subsequent generations. We have shown that fetal and neonatal exposure to nicotine results in endocrine and metabolic changes in the offspring that are consistent with those observed in type 2 diabetes. This study examines whether fetal and neonatal exposure to nicotine has transgenerational effects in the F2 offspring. Female Wistar rats were given either saline or nicotine (1 mg/kg/d) during pregnancy and lactation to create saline- and nicotine-exposed female F1 progeny. These F1 females were then bred to produce F2 offspring. We examined glucose homeostasis, serum lipids and fat pad weights, mitochondrial enzyme activity in skeletal muscle and blood pressure in these F2 offspring between 13 and 15 weeks of age. Offspring of nicotine- versus saline-exposed mothers had elevated fasting serum insulin concentrations and an enhanced total insulin response to the glucose challenge. This apparent insulin resistance was unrelated to changes in skeletal muscle mitochondrial volume or activity. The offspring of nicotine-exposed mothers also had elevated blood pressure. These data demonstrate that adverse effects of fetal and neonatal exposure to nicotine can influence aspects of metabolic risk in subsequent generations.