Maternal smoking dysregulates protein expression in second trimester human fetal livers in a sex-specific manner

Panagiotis Filis* (Corresponding Author), Nalin Nagrath, Margaret Fraser, David C Hay, John P Iredale, Peter O'Shaughnessy, Paul A Fowler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)
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CONTEXT: Maternal smoking during pregnancy has adverse effects on the offspring (e.g. increased likelihood of metabolic syndrome and infertility), which may involve alterations in fetal liver function.

OBJECTIVE: Our aim was to analyze, for the first time, the human fetal liver proteome in order to identify pathways affected by maternal smoking.

DESIGN: Fetal liver proteins extracted from elective second trimester pregnancy terminations (12-16 weeks of gestation) were divided in four balanced groups based on sex and maternal smoking.

SETTING: University of Aberdeen Patients/Participants: Livers were collected from 24 morphologically normal fetuses undergoing termination for non-medical reasons.

INTERVENTION: Maternal smoking during pregnancy.

MAIN OUTCOME MEASURES: Protein extracts were resolved by 2D-PAGE and analyzed with SameSpots software. Ingenuity Pathway Analysis was used to investigate likely roles of dysregulated proteins identified by tandem liquid chromatography/mass spectroscopy.

RESULTS: Significant expression differences between one or more groups (fetal sex and/or maternal smoking) were found in 22 protein spots. Maternal smoking affected proteins with roles in post-translational protein processing and secretion (ERP29, PDIA3), stress responses and detoxification (HSP90AA1, HSBP1, ALDH7A1, CAT) and homeostasis (FLT, ECHS1, GLUD1, AFP, SDHA). While proteins involved in necrosis, and cancer development were affected in both sexes, pathways affecting cellular homeostasis, inflammation, proliferation and apoptosis were affected in males and pathways affecting glucose metabolism were affected in females.

CONCLUSIONS: The fetal liver exhibits marked sex differences at the protein level, and these are disturbed by maternal smoking. The foundations for smoke-induced post-natal diseases are likely to be due to sex-specific effects on diverse pathways.

Original languageEnglish
Pages (from-to)E861–E870
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Issue number6
Early online date24 Mar 2015
Publication statusPublished - 2015

Bibliographical note

The staff at Grampian National Health Service Pregnancy Counseling Service were essential for collecting fetuses. We thank the Aberdeen Proteomics Core Facility (University of Aberdeen) for their expert assistance.
Support for the study was provided by the Chief Scientist Office (Scottish Executive, CZG/1/109, & CZG/4/742), National Health Service Grampian Endowments (08/02), the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement no 212885, and the Medical Research Council, UK (MR/L010011/1).


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