Prenatal Exposure to Cigarette Smoke Induces Diet- and Sex-Dependent Dyslipidemia and Weight Gain in Adult Murine Offspring

Abstract

Cardiovascular disease (CVD) affects 71 million American adults and remains the leading cause of death in the United States and Europe. Despite studies that suggest that the development of CVD may be linked to intrauterine growth or early events in childhood, little direct experimental evidence supports the notion. We investigated whether exposure to cigarette smoke in utero alters the risk of developing CVD later in life. We exposed B6C3F1 mice (via whole-body inhalation) to either filtered air or mainstream cigarette smoke (MCS, at a particle concentration of 15 mg/m3) from gestational day 4 to parturition. Adult offspring were fed a normal chow diet or switched to a high-fat diet 2 weeks before sacrifice. We measured dam and offspring body weight, plasma lipid parameters, lipoprotein subclass particle numbers and sizes, and total antioxidant capacities. Adult female mice prenatally exposed to MCS demonstrated significantly higher body weight and levels of plasma high-density lipoprotein (HDL) and low-density lipoprotein than did their air-exposed counterparts. When fed a high-fat diet for 2 weeks, males, but not females, exposed prenatally to MCS gained substantially more weight and exhibited dramatic alterations in total cholesterol and HDL levels compared with their air-exposed counterparts. These data provide, for the first time, direct experimental evidence supporting the notion that prenatal exposure to cigarette smoke affects offspring weight gain and induces a lipid profile that could alter the offspring’s risk of developing CVD later in life.