title: Prenatal exposure to carbon monoxide delays postnatal cardiac maturation.
abstract: Prenatal exposure to toxicants, such as maternal smoking, may impair cardiovascular autonomic maturation in infants. We recently showed that exposure of pregnant rats to a mild concentration of carbon monoxide (CO), a component of cigarette smoke, delays postnatal electrophysiological maturation of ventricular myocytes from newborns rats, likely predisposing to life-threatening arrhythmias. To get a comprehensive view of developmental molecular abnormalities induced, at cardiac level, by prenatal CO exposure, we used microarray analysis approach on the rat heart at 4, 7 and 20 days postnatal life. The relationship between molecular and functional alterations was investigated by assessing the ventricular expression of f-current, an electrophysiological marker of immature cardiac phenotype. Rats were prenatally exposed to 0 (CTR) or 150 p.p.m. CO and mRNA obtained from ventricular samples. Differential analysis and biological pathway analysis of microarray data were performed by using Newton's approach and the GENMAPP/MAPPFinder, respectively. The real-time RT-PCR reactions were performed by TaqMan probe-based chemistry. Freshly isolated patch-clamped ventricular cardiomyocytes were used to measure I(f). Genes and pathways controlling cell cycle and excitation-contraction coupling were significantly modified in CO-exposed rats. The higher effect was observed in cardiomyocytes harvested from 7-day-old rats, in which mRNA expression for crucial sarcomeric proteins (myosin and actin subunits, troponin I), transporters (Ca(2+) transporting ATPase) and enzymes (aldolase) were significantly downregulated. Accordingly, the molecular and functional expression of f-channels, which represents a marker of fetal ventricular phenotype, was transiently greater in CO-exposed rats (+200%) than in control ones. In conclusion, our study provides new insights into the molecular and functional mechanisms underlying cardiac maturation and its impairment by prenatal exposure to toxic components of smoking, such as CO.
authors.affiliation: Centro Interuniversitario di Medicina Molecolare e Biofisica Applicata (C.I.M.M.B.A.), University of Firenze, Firenze, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Sartiani
authors.forename: Francesca
authors.initials: F
authors.lastname: Stillitano
authors.forename: Cristina
authors.initials: C
authors.lastname: Luceri
authors.forename: Silvia
authors.initials: S
authors.lastname: Suffredini
authors.forename: Simona
authors.initials: S
authors.lastname: Toti
authors.forename: Carlotta
authors.initials: C
authors.lastname: De Filippo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cuomo
authors.forename: Maria
authors.initials: M
authors.lastname: Tattoli
authors.forename: Piero
authors.initials: P
authors.lastname: Dolara
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mugelli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cerbai
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002248:Carbon Monoxide / Q000633:toxicity*; D016000:Cluster Analysis; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000502:physiology; D005260:Female; D005333:Fetus / Q000187:drug effects*; D020869:Gene Expression Profiling; D006321:Heart / Q000187:drug effects* / Q000254:growth & development; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels / Q000235:genetics; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; C513836:HCN4 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D002248:Carbon Monoxide