Cardiovascular, carcinogenic and reproductive effects of nicotine exposure: A narrative review of the scientific literature.

The emergence of new tobacco heating products and electronic nicotine delivery systems (ENDS) is changing the way humans are exposed to nicotine. The purpose of this narrative review is to provide a broad overview of published scientific literature with respect to the effects of nicotine on three key health-related areas: 1) cardiovascular risk, 2) carcinogenesis and 3) reproductive outcomes. These areas are known to be particularly vulnerable to the effects of cigarette smoke, and in addition, nicotine has been hypothesized to play a role in disease pathogenesis. Acute toxicity will also be discussed. The literature to February 2019 suggests that there is no increased cardiovascular risk of nicotine exposure in consumers who have no underlying cardiovascular pathology. There is scientific consensus that nicotine is not a direct or complete carcinogen, however, it remains to be established whether it plays some role in human cancer propagation and metastasis. These cancer progression pathways have been proposed in models in vitro and in transgenic rodent lines in vivo but have not been demonstrated in cases of human cancer. Further studies are needed to determine whether nicotine is linked to decreased fertility in humans. The results from animal studies indicate that nicotine has the potential to act across many mechanisms during fetal development. More studies are needed to address questions regarding nicotine exposure in humans, and this may lead to additional guidance concerning new ENDS entering the market.

Transcriptome-wide analysis suggests that temporal changes in the relative contributions of hyperplasia, hypertrophy and apoptosis underlie liver growth in pregnant mice.

Maternal liver undergoes structural and metabolic changes during pregnancy to meet the demands of the developing fetus. In rodents, this involves increased liver weight, but the mechanism remains unclear. To address this, we analyzed the histology, gene expression, and DNA methylation of livers of nonpregnant and pregnant C57/BL6 mice. Gestational liver growth in pregnant mice was accompanied by increased hepatocyte area and lower cell density (days 14 and 18). Expression of cell proliferation markers was increased on days 14 and 18. A total of 115 genes were differentially expressed on day 14 and 123 genes on day 18 (79 on both days). Pathway analysis indicated that pregnancy involves progressive increase in cell proliferation and decreased apoptosis. This was confirmed using archived data from the FVB wild-type mouse liver transcriptome. Four differentially DNA methylated and two differentially DNA hydroxymethylated regions identified on days 14 and 18 by methylome-wide analysis, but were not associated with altered gene expression. Long interspersed nuclear element-1 hypomethylation on days 14 and 18 was accompanied by increased ten-eleven translocase-2 and decreased DNA methyltransferase 3a and 3b expression. These findings suggest that gestational liver growth involves increased mitosis and hypertrophy, and decreased apoptosis contingent on pregnancy stage. Such changes may involve repetitive sequence, but not gene specific, DNA methylation.