||Cigarette smoking alters sialylation in the Fallopian tube of women, with implications for the pathogenesis of ectopic pregnancy
Nio-Kobayashi, Junko ,
Abidin, Hazirah B. Z. ,
Brown, Jeremy K. Iwanaga, Toshihiko ,
Horne, Andrew W.Duncan, W. Colin
Molecular Reproduction and Development
1091 , 2016-12 , Wiley
The expression of sialyltransferases decreases during tubal ectopic pregnancy in women and cigarette smoking alters the expression of ST6GAL1 and ST3GAL5, potentially resulting in a decreased tubal transport and an increased receptivity for blastocysts.
We recently reported potential involvement of galectin-1 and galectin-3, β-galactoside-binding lectins, in pathogenesis of tubal ectopic pregnancy. However, the precise role of galectins and their ligand glycoconjugates remain unclear. Sialylation serves surface negativity to block blastocyst implantation, and α2,6-sialylation on terminal galactose catalyzed by a sialyltransferase, ST6GAL1, inhibits the binding of galectin-1, which is increased in expression level during tubal ectopic implantation. We here investigated the expression of α2,3- and α2,6-galactoside sialyltransferases (ST3GAL1-6 and ST6GAL1-2) and the localization of sialic acids in the Fallopian tube from women with or without ectopic implantation. The expression level of ST6GAL1 was higher in the mid-secretory phase than the proliferative phase (P<0.0001) of non-pregnant women. In the Fallopian tube with ectopic implantation, ST6GAL1 was lower (P<0.0001) as were ST3GAL3 (P=0.0029), ST3GAL5 (P=0.0089), and ST3GAL6 (P=0.0018). Cigarette smoking, a major risk factor for tubal ectopic pregnancy, was associated with a reduced mid-secretory phase expression of ST6GAL1 (P=0.0298) and elevated expression of ST3GAL5 (P=0.0006), an enzyme known to be involved in ciliogenesis. Both α2,3- and α2,6-sialic acids were localized to the surface of the Fallopian tube epithelium. Sialic acid-containing ciliated inclusion cysts, which are known to be associated with abnormal ciliogenesis, were observed within the epithelium, and the number of cysts increased (P=0.0177) in women who smoked, suggesting that abnormal ciliogenesis is associated with smoking. These results suggest that cigarette smoking alters sialylation in the Fallopian tube epithelium and potentially involved in a decreased tubal transport and an increased receptivity for blastocyst in human Fallopian tube.