title: Cigarette smoking alters sialylation in the Fallopian tube of women, with implications for the pathogenesis of ectopic pregnancy.
abstract: Sialylation creates a negative charge on the cell surface that can interfere with blastocyst implantation. For example, α2,6-sialylation on terminal galactose, catalyzed by the sialyltransferase ST6GAL1, inhibits the binding of galectin-1, a β-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 α2,3- and α2,6-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. α2,3- and α2,6-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. Mol. Reprod. Dev. 83: 1083-1091, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: 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: Jeremy K
authors.initials: JK
authors.lastname: Brown
authors.affiliation: Laboratory of Histology and Cytology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iwanaga
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: W Colin
authors.initials: WC
authors.lastname: Duncan
mesh_terms: D000293:Adolescent; D000328:Adult; D005187:Fallopian Tubes / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012799:Sialyltransferases / Q000096:biosynthesis*; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid