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 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 language | English |
|---|---|
| Pages (from-to) | E861–E870 |
| Number of pages | 10 |
| Journal | Journal of Clinical Endocrinology and Metabolism |
| Volume | 100 |
| Issue number | 6 |
| Early online date | 24 Mar 2015 |
| DOIs | |
| Publication status | Published - 2015 |
Bibliographical note
AcknowledgmentsThe 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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- Maternal Smoking Dysregulates Protein Expression in Second Trimester Human Fetal Livers in a Sex-Specific Manner
This article has been published under the terms of the Creative Commons Attribution License (CC-BY; https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s). - See more at: http://press.endocrine.org/doi/10.1210/jc.2014-3941#sthash.FTpX3JJP.dpuf
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Paul Alfred François Fowler
- School of Medicine, Medical Sciences & Nutrition, Molecular and Cellular Function
- School of Medicine, Medical Sciences & Nutrition, Applied Medicine - Chair in Translational Medical Sciences
- School of Medicine, Medical Sciences & Nutrition, Institute of Medical Sciences
Person: Academic