Smoking Out Fetal Growth Restriction

Abstract

Researchers have uncovered a mechanism behind one of the most damaging effects of maternal smoking—fetal growth restriction [1]. It seems that smoking boosts expression of a signaling molecule—secreted frizzled-related protein 1 (sFRP1)—that suppresses placental growth and development. The findings may help explain why infants of mothers who smoke weigh, on average, 200–400 g less than the infants of nonsmokers. Alice Wang et al. first found that sFRP1 mRNA levels were highly elevated in the placentas from smoking mothers who gave birth to babies with severe growth restriction. An extracellular antagonist of WNT signaling, sFRP1 is known to be involved in placental development. The researchers next overexpressed sFRP1 in pregnant mice, and observed defects in the placenta and decreased proliferation of labyrinthine trophoblasts. Exposing a trophoblast cell line to a carbon monoxide analog reduced WNT signaling, increasing sFRP1 mRNA expression and decreasing cellular proliferation. The researchers also exposed pregnant mice to the carbon monoxide analog, and found that these mice gave birth to underweight pups—though the effects on WNT and sFRP1 signaling remain to be explored. Other studies have hinted at other mechanisms behind fetal growth restriction in smoking mothers. Carbon monoxide has a great affinity for hemoglobin and can cause fetal hypoxia, and uterine and umbilical arteries constrict in response to tobacco smoke. Perhaps some of these factors may also affect sFRP1 expression. Smoking during pregnancy is a growing public health threat, and can also cause lung problems, cognitive effects, and other health issues in children. While smoking rates in the United States are on the decline, tobacco companies are tapping into the vast potential market in undeveloped countries—some of which, like Indonesia, currently have high rates of smoking in males but very low rates in females. The United States has yet to ratify the World Health Organization Framework Convention on Tobacco Control, which provides some counterweight to the growing number of lawsuits by tobacco companies claiming that country-wide efforts at tobacco control violate trade laws (http://www.nytimes.com/ 2013/12/13/health/tobacco-industry-tactics-limit-poorernations-smoking-laws.html).