Perinatal nicotine-induced transgenerational asthma

Asthma is a major public health hazard worldwide. Its transgenerational inheritance has been inferred from epidemiological studies. More recently, using nicotine as a proxy for maternal smoking, we have demonstrated that an asthma-like phenotype can be inherited by rat offspring for up to two generations, i.e., multigenerationally, after the initial intrauterine exposure. We hypothesized that asthma transmission to offspring following perinatal nicotine exposure is not restricted up to F-2 generation, but it also extends to subsequent generations. To test this hypothesis, using a well-established rat model of nicotine exposure-induced childhood asthma, we determined if perinatal nicotine exposure of F-0 gestating dams would transmit asthma transgenerationally to F-3 offspring. We now extend our findings to third-generation offspring, including abnormal pulmonary function, particularly as it relates to the occurrence in the upper airway exclusively in males, and to its effects on molecular functional markers (fibronectin and peroxisome proliferator-activated receptor gamma), previously shown to be consistent with the asthma phenotype, herein expressed in fibroblasts isolated from the lung. These data, for the first time, demonstrate the transgenerational transmission of the asthma phenotype to F-3 offspring following perinatal nicotine exposure of F-0 dams.