Cigarette Smoking Alters Sialylation in the Fallopian Tube of Women, With Implications for the Pathogenesis of Ectopic Pregnancy

Sialylation creates a negative charge on the cell surface that can interfere with blastocyst implantation. For example, alpha 2,6-sialylation on terminal galactose, catalyzed by the sialyltransferase ST6GAL1, inhibits the binding of galectin-1, a beta-galactoside-binding lectin. We recently reported the potential involvement of galectin-1 and -3 in the pathogenesis of tubal ectopic pregnancy; however, the precise role of galectins and their ligand glycoconjugates remain unclear. Here, we investigated the expression of the genes encoding alpha 2,3- and alpha 2,6-galactoside sialyltransferases (ST3GAL1-6 and ST6GAL1-2) and the localization of sialic acids in the Fallopian tube of women with or without ectopic implantation. ST6GAL1 expression was higher in the mid-secretory phase than the proliferative phase of non-pregnant women (P<0.0001), whereas ST6GAL1 (P<0.0001), ST3GAL3 (P=0.0029), ST3GAL5 (P=0.0089), and ST3GAL6 (P=0.0018) were all lower in Fallopian tubes with ectopic implantations. alpha 2,3- and alpha 2,6-sialic acids, however, both remained enriched on the surface of Fallopian tube epithelium. Cigarette smoking, a major risk factor for tubal ectopic pregnancy, was associated with reduced mid-secretory-phase expression of ST6GAL1 (P=0.0298), but elevated expression of ST3GAL5 (P=0.0006), an enzyme known to be involved in ciliogenesis. Indeed, sialic acid-containing ciliated inclusion cysts, which are associated with abnormal ciliogenesis, were observed within the epithelium at a higher frequency in women who smoked (P=0.0177), suggesting that abnormal ciliogenesis is associated with smoking. Thus, cigarette smoking alters sialylation in the Fallopian tube epithelium, and is potentially a source of decreased tubal transport and increased receptivity for blastocyst in the human Fallopian tube. (C) 2016 Wiley Periodicals, Inc.