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Smoking disrupts protein expression in human fetal livers

Researchers found that maternal smoking greatly disrupted the protein expression and pathways of human fetal livers in the second trimester, according to data published in The Journal of Clinical Endocrinology and Metabolism.

“Given the importance of the fetal liver to human fetal development and its susceptibility to maternal smoking, we have, for the first time, used a proteomics approach to identify proteins and pathways that are dysregulated in the human fetal liver by maternal smoking,” the researchers wrote.

Paul A. Fowler

Researchers, including Paul A. Fowler, BSc Hons, PhD, FSB, of the Institute of Medical Sciences, division of applied medicine, University of Aberdeen, in Scotland, analyzed 55 human fetal liver extracts from 24 elective pregnancy terminations between 12 weeks and 17 weeks, and divided them into groups according to sex and validated smoke exposure. The groups consisted of 14 male controls, 13 smoke-exposed males, 15 female controls and 13 smoke-exposed females. Of these patients, six from each group were “chosen for proteomics” so each group was comprised of one pregnancy in the 12th week, two in their 13th week, one in the 14th week, one in the 15th week, and one in the 16th to 17th weeks for fetal liver protein extracts, according to the research.

Each group had 100 µg of protein extracts taken from each fetal liver and combined to remove contaminants. The proteins were resolved using 2D polyacrylamide gel electrophoresis (2D-PAGE) and analyzed with Progenesis SameSpots (Nonlinear Dynamics) software.

Overall, the research stated that 494 fetal liver protein spots showed reproducibility in replicated 2D-PAGE gels, of which 22 showed spot volume differences between at least two of the four groups.

“Maternal cigarette smoking during pregnancy causes changes in the amounts of important proteins in the livers of their fetuses,” Fowler told Healio.com/Hepatology. “Some of these changes were sex-specific or indeed, were the loss of sex differences seen in fetuses not exposed to cigarette smoke. The proteins have functions within the fetal liver to detoxify chemicals or control how the liver would respond to stress.”

In both sexes, smoking affected the ECHS1, ALDH7A1, TPI1, KRT8 and ERP29 fetal liver proteins. In females, AFP, PGK1, KRT8, GLUD1, CAT, CRYL1, USP5, HSP90AA1, and SDHA liver proteins were affected compared with the male liver proteins SPRYD4, FTL1, PNP, PDIA3, HSPB1 and EEF1B2. Protein pathways to both necrosis and cancer development were apparent in both sexes. However, pathways affecting cellular homeostasis, inflammation, proliferation and apoptosis were affected in males, whereas pathways affecting glucose metabolism were affected in the female fetus livers.

 “Our findings suggest that changes in the protein profile of the human fetal liver is an important way in which the cigarette exposure in the womb is translated into ill health, such as liver disease, cancer and metabolic syndrome in adulthood,” Fowler said. “The next step is to find biomarkers for these changes that could be measured at birth as a first step towards developing personalized medical and lifestyle strategies to reduce the likelihood of later ill health.” – by Melinda Stevens

Disclosures: The researchers report no relevant financial disclosures.