How Nicotine Harms the Embryo

Research shows that nicotine has far-reaching negative effects on the development of human embryos at the single-cell level. Single-cell RNA sequencing of embryoid bodies derived from human embryonic stem cells (hESCs) revealed that three weeks of nicotine exposure disrupts communication between cells, reduces cell survival, and alters the expression of genes that regulate important functions such as the contraction of heart muscle cells.

The Dangerous Effects of Nicotine During Pregnancy

These findings are particularly important because they provide a scientific basis for educating the public, especially young women, not to smoke during pregnancy or when planning to start a family. Nicotine, found in products such as tobacco, e-cigarettes, and nicotine gum, can have far-reaching harmful effects on various organs of a developing embryo during pregnancy. Nicotine use during pregnancy is a known risk factor for birth defects such as miscarriages, growth disorders, and premature births. It is closely linked to long-term negative effects on the neurobehavior, cardiovascular system, respiratory system, endocrine system, and metabolism of offspring. Nicotine, the main chemical component of tobacco smoke, is primarily responsible for the increased risk. Unfortunately, the introduction and spread of new nicotine-containing tobacco products such as e-cigarettes are reversing recent progress in reducing tobacco use.

A large body of research has demonstrated the negative effects of nicotine in animals, primarily in rodent models. Animal studies have shown that nicotine exposure during pregnancy has harmful effects on fetal development. However, due to differences between species, it remains unclear whether these research findings can be extrapolated to humans. While other studies have examined nicotine toxicity in human cells using bulk RNA sequencing analyses, these conventional studies have not allowed researchers to examine the effects at the single-cell level. As a result, the effects of nicotine on human embryonic development and the underlying molecular mechanisms remain poorly understood.

Embryonic Development is Negatively Affected as Early as the Preimplantation Stage

To overcome these limitations, scientists at Stanford University School of Medicine used single-cell RNA sequencing to analyze the effects of 21 days of nicotine exposure on the transcriptomes of a total of 12,500 cells generated from hESC-derived embryoid bodies. These are 3D aggregates of different types of pluripotent cells that give rise to the brain, heart, liver, blood vessels, muscles, and other organs. They found that cell survival rates decreased, suggesting that nicotine can affect embryonic development even at the preimplantation stage. Nicotine exposure also reduced the size of the embryoid bodies, increased the content of harmful molecules called reactive oxygen species, and led to abnormal formation and differentiation of the embryoid bodies. In addition, nicotine exposure altered the cell cycle in a variety of precursor cells differentiated from hESCs and caused dysregulated cell-to-cell communication, another adverse effect that has not yet been well studied.

This is important because smoking and nicotine have been shown to increase pathological risk in endocrine, reproductive, respiratory, cardiovascular, and neurological systems, which rely on complex and dynamic interactions between multiple cell types for their homeostasis and function. The researchers also found that nicotine exposure leads to altered expression of genes involved in metal toxicity and mitochondrial function, brain malformations and mental retardation, muscle development and disease, lung disease, and Ca2+-associated arrhythmias that impair the contractility of heart muscle cells.