Maternal Smoking during Pregnancy and Changes in Prostaglandin Enzymes in the Human Fetus.

Aikaterini Zafeiri, Panagiotis Filis, Sophie Shaw, John P. Iredale, Madeleine J. Swortwood, Rod T. Mitchell, David C. Hay, Peter J. O'Shaughnessy, Paul A. Fowler

Research output: Contribution to journalAbstractpeer-review


Introduction: Prostaglandins (PGs) are inflammatory modulators with
important homeostatic and regenerative roles in the liver and their
dysregulation can lead to pathological outcomes. Over 20% of pregnant
women smoke and smoke constituents that reach the fetal liver can disrupt
PG synthesis, contributing to negative outcomes for the offspring. In
this study we examined the effect of maternal smoking on PG synthesis
pathway in the human fetal liver.
Methods: RNA was extracted from 80 human fetal livers (12-19 wks
of gestation) from elective terminations of normal pregnancies (NHS
Grampian, REC 04/S0802/21). mRNA transcripts were quantified using
Illumina RNAseq sequencing. Statistical analyses employed generalised
linear models to examine interrelationships between fetal age, sex and
smoke exposure (validated by fetal cotinine levels) to determine the
effect of maternal smoking in the expression of PG biosynthetic enzymes.
Results: Compared with fetuses from non-smoking mothers, exposure
was associated with: 1) male-specific increase in PLA2G2A, PTGS2,
PTGIS and PTGIR at ≥16 gestation wks, 2) female-specific increase in
PLA2G2A, PTGIS and PTGIR at 14-16 gestation wks. Changes in those
enzymes suggest increased PG production potentially establishing an
inflammatory environment in the fetal liver. Increase in the prostacyclin
(protective PG) receptor PTGIR suggests compensatory liver mechanisms
including cytoprotection and vasodilation to counteract inflammation
(Figure 1). Overall, an upregulation of this part of the PG pathway was
found in fetuses of both sexes at different gestational stages. Our findings
are being followed-up in a cohort of 254 human fetal livers.
*Figure(s) will be available online.
Conclusion: Maternal smoking disrupts liver inflammatory homeostasis
via the alteration of PG signalling, potentially contributing to
developmental perturbations and disease predisposition. Our observations
are also relevant to alterations in PG signalling in the fetal organs caused
by commonly used over-the-counter analgesics during pregnancy.
Identification of the exact point/s of the effect would further our current
knowledge of how in-utero toxicant exposure can lead to adverse health
Original languageEnglish
Article numberF-103
Pages (from-to)244A-244A
Number of pages1
JournalReproductive Sciences
Publication statusPublished - Mar 2019
Event66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI) - Paris, France
Duration: 12 Mar 201916 Mar 2019

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