title: The association between smoking and ectopic pregnancy: why nicotine is BAD for your fallopian tube.
abstract: Epidemiological studies have shown that cigarette smoking is a major risk factor for tubal ectopic pregnancy but the reason for this remains unclear. Here, we set out to determine the effect of smoking on Fallopian tube gene expression. An oviductal epithelial cell line (OE-E6/E7) and explants of human Fallopian tubes from non-pregnant women (n = 6) were exposed to physiologically relevant concentrations of cotinine, the principle metabolite of nicotine, and changes in gene expression analyzed using the Illumina Human HT-12 array. Cotinine sensitive genes identified through this process were then localized and quantified in Fallopian tube biopsies from non-pregnant smokers (n = 10) and non-smokers (n = 11) using immunohistochemistry and TaqMan RT-PCR. The principle cotinine induced change in gene expression detected by the array analysis in both explants and the cell line was significant down regulation (P<0.05) of the pro-apoptotic gene BAD. We therefore assessed the effect of smoking on cell turnover in retrospectively collected human samples. Consistent with the array data, smoking was associated with decreased levels of BAD transcript (P<0.01) and increased levels of BCL2 transcript (P<0.05) in Fallopian tube biopsies. BAD and BCL2 specific immunolabelling was localized to Fallopian tube epithelium. Although no other significant differences in levels of apoptosis or cell cycle associated proteins were observed, smoking was associated with significant changes in the morphology of the Fallopian tube epithelium (P<0.05). These results suggest that smoking may alter tubal epithelial cell turnover and is associated with structural, as well as functional, changes that may contribute to the development of ectopic pregnancy.
authors.affiliation: MRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Horne
authors.affiliation: MRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Brown
authors.affiliation: MRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom ; Laboratory of Histology and Cytology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Nio-Kobayashi
authors.affiliation: MRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Hazirah B Z
authors.initials: HB
authors.lastname: Abidin
authors.affiliation: MRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Zety E H A
authors.initials: ZE
authors.lastname: Adin
authors.affiliation: MRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Lyndsey
authors.initials: L
authors.lastname: Boswell
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Penicuik, United Kingdom.
authors.forename: Stewart
authors.initials: S
authors.lastname: Burgess
authors.affiliation: Department of Obstetrics and Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Kai-Fai
authors.initials: KF
authors.lastname: Lee
authors.affiliation: MRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: W Colin
authors.initials: WC
authors.lastname: Duncan
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003367:Cotinine / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005187:Fallopian Tubes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005731:Ganglionic Stimulants / Q000494:pharmacology; D006801:Humans; D007124:Immunoenzyme Techniques; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology*; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects*; D055815:Young Adult; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C494819:BAD protein, human; D005731:Ganglionic Stimulants; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051025:bcl-Associated Death Protein; D009538:Nicotine; D003367:Cotinine