March 15, 2012
Scientists have gained insight into how second-hand tobacco smoke damages the earliest stages of human embryonic development.
The UCSF-led team made its discovery by studying the impact of smoke on human embryonic stem cells as they differentiated, or specialized into various cell types, in the culture dish.
They determined that both nicotine and non-nicotine components of tobacco smoke impede the cells from specializing into a broad range of cell types, including those of the blood, heart, musculoskeletal systems and brain.
They also established that at least some of the impact was mediated through several molecular pathways known to play a role in differentiation.In one of the pathways, the toxins dramatically increased the activity of a key gene that keeps embryonic stem cells in an undifferentiated state, suggesting that its disruption might be responsible for much of the delay seen in embryonic development.
Scientists already know that in utero exposure to tobacco smoke increases the risk of a child being born pre-term and underweight, conditions associated with an increased risk of respiratory distress syndrome, cardiovascular defects, cleft lip and palate, immunodeficiency and Sudden Infant Death Syndrome. They also know that exposure is associated with increased risk of childhood leukemia, lymphoma and brain tumors, and, later in life, attention deficit and hyperactivity disorders, as well as other behavioral and psychological problems.
However, until now, they’ve known little about the underlying molecular mechanisms responsible for these pathologies. The study, reported in the April issue of Differentiation, provides some of the first hard evidence.
“We know second-hand smoke exposure is bad for the developing fetus, causing everything from heart defects to childhood cancer, but we haven’t understood why,” said senior author Harold S. Bernstein, MD, PhD, who is a UCSF professor of pediatrics and a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF. “We hope the findings will be a launching pad for further investigations on the impact on fetal development at the cellular level.”