Poster Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Elevated galectin-7 is predictive of miscarriage and preelampsia and detrimental to trophoblast function during implantation and placentation. (#342)

Ellen M Menkhorst 1 , Michelle Van Sinderen 1 , Thilini Gamage 1 , Carly Cuman 1 , Tu'uhevaha Kaitu'u-Lino 2 , Evdokia Dimitriadis 1
  1. MIMR-PHI Institute, Clayton, VIC, Australia
  2. University of Melbourne, Melbourne, VIC, Australia

There is very little known of the mechanisms leading to recurrent miscarriage and preeclampsia although defective implantation and placentation respectively are thought central to these diseases. Galectins are expressed at the fetal-maternal interface and regulate many cell functions important for placentation including adhesion and migration. However, the localization and role of galectin-7 is unknown. We hypothesized galectin-7 is expressed at the fetal-maternal interface, detectable in maternal serum and has functional roles in trophoblast invasion.

Immunohistochemistry localised galectin-7 to endometrium and 1st trimester placenta. ELISA determined galectin-7 maternal serum levels. We used HTR8/Svneo and primary human endometrial epithelial and trophoblast cells to determine the effect of exogenous galectin-7 on proliferation, adhesion, invasion, outgrowth and intracellular signalling as well as the effect of hypoxia on galectin-7 expression.

Galectin-7 immunolocalized to endometrial epithelial cells in non-pregnant endometrium, and syncytiotrophoblast, extravillous trophoblast and glandular epithelium in placenta/decidua. Endometrial epithelial immunostaining was significantly elevated in the non-pregnant endometrium of women with a history of miscarriage (n=28; p<0.05).

Galectin-7 serum levels were elevated in women who subsequently miscarried (blood collected 6 weeks gestation; control: 3.2+0.7µg/ml, n=20; miscarriage: 9.7+2.6µg/ml, n=5; p<0.05) or developed preeclampsia (blood collected 10-12 weeks gestation; control: 1.0+0.1µg/ml, n=6; preeclamptic: 1.3+0.1µg/ml n=10; p<0.05) compared to healthy gestation-matched controls.

Culture under low oxygen conditions elevated galectin-7 mRNA in 1st trimester placental villi (2%O2: 9.5+3.0fold vs 20%O2: 1.0fold; n=5; p<0.05). Exogenous galectin-7 phosphorylated STAT3 and impaired endometrial epithelial-trophoblast adhesion (100 vs 66.3+7.3%; n=3; p<0.05), trophoblast outgrowth from placental villi (100 vs 62+5%; n=3; p<0.05) and EVT invasion (100 vs 66%; n=2).

Our data suggests that elevated galectin-7 levels in miscarriage and preeclampsia are induced by placental oxidative stress and inhibit trophoblast invasion (likely via pSTAT3) leading to impaired implantation and/or placental development. Galectin-7 may be useful as a prospective serum biomarker of miscarriage and preeclampsia.