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.

Cigarette smoking alters sialylation in the Fallopian tube of women, with implications for the pathogenesis of ectopic pregnancy

“…These data suggest that the increased number of ciliated cysts reflects impaired ciliogenesis in the Fallopian tube epithelium of women who smoked. Cigarette smoking is a major risk factor for tubal ectopic implantation (Shaw et al, ), and we previously showed that luminal epithelial cells of the Fallopian tube of women who smoke have altered rates of cell turnover and a higher potential to lose cilia (Horne et al, ). Results from this study provide additional evidence that smoking changes the structure of the Fallopian tube epithelial cells.…”

Substance Use in the Perinatal Period

“…Additionally, mothers exhibiting persistent smoking patterns during the second and third trimesters had higher depressive symptomatology and stress relative to non-persistent smokers [36]. Recent research continues to demonstrate that tobacco and nicotine exposure are associated with adverse pregnancy outcomes, including damage to the umbilical cord structure [37], miscarriage [38], increased risk for ectopic pregnancy [39] and preterm delivery [23,40]. Smoking in pregnancy is also associated with increased infant morbidity and mortality [8,41-45], and second-hand smoke is associated deleterious health effects on newborns, which include increased risk for respiratory and ear infections, sudden infant death syndrome, behavioral dysfunction and cognitive impairment [46].…”

Ectopic Pregnancy: Diagnosis, Prevention and Management

“…BAD-and BCL2-specific immunolabeling was localized to Fallopian tube epithelium. So, smoking may alter tubal epithelial cell turnover and is associated with structural, as well as functional, changes that may contribute to the development of EP [50]. Moreover, cigarette smoking increases transcription of prokineticin receptor 1 (PROKR1), a G-protein-coupled receptor [49].…”