Maternal smoking dysregulates protein expression in second trimester human fetal livers in a sex-specific manner. Maternal smoking and the fetal liver proteome

Panagiotis Filis, Nalin Nagrath, Margaret Fraser, David Hay, John Iredale, Peter O'Shaughnessy, Paul A Fowler

Research output: Contribution to journalArticlepeer-review

Abstract

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 Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation 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 postnatal diseases are likely to be due to sex-specific effects on diverse pathways.
Original languageEnglish
Article numberjc20143941.
JournalJournal of Clinical Endocrinology & Metabolism
DOIs
Publication statusPublished - 24 Mar 2015

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