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 þ 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 ( þ 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.

Cardiovascular and metabolic influences of fetal smoke exposure

“…Fetal vasoconstriction and impaired blood flow may lead to suboptimal hemodynamic stimulus for placental and fetal vascular development [47, 48]. Other toxins from maternal smoking also lead to reduced placental and fetal perfusion [48–51]. Some studies suggest that nicotine directly influences cell proliferation and differentiation, hereby affecting neural cell survival and the development of fetal neurotransmitter systems [49].…”

“…Another teratogenic element in smoking is carbon monoxide, which is rapidly absorbed in the blood where it binds to haemoglobin and forms carboxyhaemoglobin which results in hypoxia, and might be teratogenic and fetotoxic [50]. Animal studies show a direct negative effect of prenatal carbon monoxide exposure on cardiac maturation [51]. Cadmium is also a toxic constituent of tobacco smoke.…”

A perspective on SIDS pathogenesis. The hypotheses: plausibility and evidence

“…Because many clues indicate the heart could be the final weakness in the SIDS story, the work of Sartiani et al . [151] could confirm a link between smoking in pregnancy, fetal exposure to carbon monoxide and abnormal cardiac development.…”

SIDS Risk Factors: Time for New Interpretations. The Role of Bacteria

“…The work of Sartiani et al (2010) could provide answers to the link between smoking in pregnancy, and fetal exposure to carbon monoxide and abnormal cardiac development, given that SIDS babies' hearts show developmental abnormalities (Naeye et al 1976). A study of 33,034 infants found that 50% of infants who died of SIDS had a prolonged QT interval in the first week of life (Schwartz et al 1998).…”