Maternal smoking is associated with mitochondrial DNA depletion and respiratory chain complex III deficiency in placenta

Abstract

Maternal smoking during pregnancy is often associated with a decrease in placental function, which might lead to intrauterine growth retardation. Because tobacco is known to alter the mitochondrial respiratory function in cardiomyocytes and lung tissue, we hypothesized that placental mitochondrial function could be altered by maternal smoking. Placental mitochondria from 9 smoking and 19 nonsmoking mothers were isolated by differential centrifugation. Mitochondrial oxygen consumption was measured by polarography, and the enzymatic activity of each complex of the electron transport chain was assessed by spectrophotometry. In addition, the relative content in mitochondrial DNA (mtDNA) was determined by real-time quantitative PCR in placentas from seven smoking and seven nonsmoking mothers. We observed a 29% reduction in the enzymatic activity of complex III in the placental mitochondria from smokers compared with nonsmokers (P = 0.03). The relative content of mtDNA (with respect to the beta-globin gene) was reduced by 37% in the placental tissue from smokers compared with nonsmokers (P < 0.02). Both the enzymatic activity of complex III and mtDNA content were inversely related with the daily consumption of cigarettes, and mtDNA content was correlated with cord blood insulin-like growth factor-binding protein-3 (r = 0.74, P < 0.01), a marker of fetal growth. These results show that maternal smoking is associated with placental mitochondrial dysfunction, which might contribute to restricted fetal growth by limiting energy availability in cells.

In vitro cell-toxicity screening as an alternative animal model for coral toxicology: effects of heat stress, sulfide, rotenone, cyanide, and cuprous oxide on cell viability and mitochondrial function

“…For example, short-term, acute cigarette smoking does not cause mortality, but it does adversely affect mitochondrial function (Miró et al 1999;Smith et al 1993;Alonso et al 2004). Prolonged depression of mitochondrial function from this exposure can manifest into a number of physiological disorders, as well as morbid pathologies (e.g., Bouhours-Nouet et al 2005;van der Toorn et al 2007). Hence, changes in sub-cellular systems may cause changes to higher order processes, such as immuno-competence, reproduction, and growth (Downs 2005).…”

Polycyclic aromatic hydrocarbons in maternal and cord blood plasma.

“…Other recent studies have linked components of tobacco smoke, especially PAH, to a variety of enzymatic, inflammatory and cellular changes in the placenta and the fetus. (43,(182)(183)(184)(185)(186)(187)(188)(189)(190) Unlike a singular event that may or may not coincide with a critical epoch, maternal smoking during pregnancy represents chronic exposure of the fetus to the thousands of compounds in tobacco smoke many times a day over multiple days or weeks. Repeated exposure across numerous critical windows may amplify the resulting effect from very early in gestation.…”

Mitochondrial toxicity of tobacco smoke and air pollution

“…Active and passive cigarette smoke decrease mitochondrial respiration and membrane potential leading to decreased ATP content and increased oxidant production in a variety of tissues in a dose- and time-dependent manner 15–21, 23, 25, 27–30, 32, 33, 37, 52, 91, 92 . Mitochondria are rich in enzymes with active sites easily modified and inactivated by ROS/RNS from the inhalation of tobacco smoke, or from oxidant generation within the mitochondrion (please see Bonini review herein, “ Oxidative signaling in mitochondrial homeostasis ” Chapter 4).…”

“…Environmental toxicant exposure induces changes in mitochondrial respiration and metabolism 15–25 , oxidant generation 26–31 , mitochondrial DNA ( mtDNA ) damage and copy number 25, 29, 30, 32–36 , network formation and structure 19, 37–39 , clearance of dysfunctional mitochondria through mitophagy 40 , apoptosis 24 , and reduction-oxidation ( redox ) signaling 24, 27 . Mitochondria contain many iron-rich enzymes making the proteins within the organelle particularly sensitive to oxidant inactivation 41–43 .…”