Tobacco smoke affects early human embryonic development

By Jennifer O'Brien

(Medical Xpress) -- 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 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 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 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 , cardiovascular defects, , and . They also know that exposure is associated with increased risk of , lymphoma and , and, later in life, attention deficit and hyperactivity disorders, as well as other behavioral and .

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.

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“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.”

In the study, led by Water Liszewski, who was at the time a technician in the Bernstein lab, the scientists took a two-pronged approach. First, they extended the analysis of gene activity in umbilical cord stem cells previously examined by their University of Connecticut co-authors, determining that tobacco smoke increased the activity of genes that delay the development of mesoderm – the layer of tissue that gives rise to blood, musculoskeletal and cardiovascular systems – as well endoderm and ectoderm, the two other layers of embryonic cells that give rise to the tissues of the body.

Next, they exposed human embryonic stem cells in the culture dish either to tobacco smoke or nicotine at concentrations found in fetal blood. They did so while the cells were spontaneously specializing.

Then, using microarray analysis, quantitative polymerase chain reaction (PCR) and immunoblot analysis, they assessed gene activity at key time points in the process of specialization. They discovered that both nicotine and non-nicotine components of tobacco smoke increased the activity of genes that hold embryonic stem cells in a pluripotent, or undifferentiated, state. They also showed that the toxins increased activity of genes that delay the development of the three germ layers.

Finally, they assessed gene expression in three stem cell differentiation pathways, known as Notch, canonical Wnt and TGF-β. They determined that sentinel genes in each pathway were over expressed, but one most prominently: Expression of the Nodal gene was 50- to 75-fold higher in nicotine and tobacco smoke-exposed cells, respectively, than in untreated cells.

The findings reveal the widespread impact of both nicotine and non-nicotine components of on early , according to Bernstein.

They also highlight the power of as a model of human development. “They allowed us to get at questions which, until now, we couldn’t examine in humans,” he said.

First author Liszewski currently is a second-year medical student at Tulane University School of Medicine. Other co-authors of the study are Carissa Ritner, Julian Aurigui, Sharon S.Y. Wong of UCSF, and Naveed Hussain, Winfried Krueger and Cheryl Oncken of the University of Connecticut.

The study was supported by funds from the Connecticut Department of Health and the University of Connecticut General Clinical Research Center, a grant from the National Heart, Lung and Blood Institutes, a gift from the Polin Foundation, and funds from the Department of Pediatrics, University California, San Francisco.

More information: The paper: www.sciencedirect.com/science/… ii/S0301468111002295

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dogbert
not rated yet Mar 16, 2012
B.S.

1) Embryos developed in a culture dish are prone to damage from a multitude of environmental assaults. That is why viable human embryos are developed in a uterus.

2) Under natural circumstances, a human embryo is never exposed to light, air, dust, ozone, smoke or any of an innumerable list of substances.

That an embryo might be harmed by the direct application of smoke is no more surprising than that an embryo might be harmed by the direct application of chlorine bleach.
tadchem
not rated yet Mar 16, 2012
The article seems to confound "tocbacco smoke" with "certain substances found in tobacco smoke."
It would also be interesting to know how the dose exposures for the in vitro stem cells were compared to those for in vivo embryos.
"Alle Ding' sind Gift, und nichts ohn' Gift; allein die Dosis macht, daß ein Ding kein Gift ist." - Paracelsus
Tausch
not rated yet Mar 17, 2012
Too much of anything is bad.
What a weird reality our existence allows us to experience - anthropologically.

As if the equal sign or symmetry is more than a human construct.
Reducing the universe to a tight rope act - balance the purpose.

Immortals constantly ask us about our demise. We answer - if we answer at all - with fervor. Religion fervor.

Forgive the digression to tadchem's German prose.