Evidence for Differential Glycosylation of Trophoblast Cell Types

Qiushi Chen,Poh-Choo Pang,Marie E Cohen,Mark S Longtine,Danny J Schust,Stuart M Haslam,Sandra M Blois,Anne Dell,Gary F Clark

doi:10.1074/mcp.m115.055798

Abstract

Human placental villi are surfaced by the syncytiotrophoblast (STB), with a layer of cytotrophoblasts (CTB) positioned just beneath the STB. STB in normal term pregnancies is exposed to maternal immune cells in the placental intervillous space. Extravillous cytotrophoblasts (EVT) invade the decidua and spiral arteries, where they act in conjunction with natural killer (NK) cells to convert the spiral arteries into flaccid conduits for maternal blood that support a 3-4 fold increase in the rate of maternal blood flow into the placental intervillous space. The functional roles of these distinct trophoblast subtypes during pregnancy suggested that they could be differentially glycosylated. Glycomic analysis of these trophoblasts has revealed the expression of elevated levels of biantennary N-glycans in STB and CTB, with the majority of them bearing a bisecting GlcNAc. N-glycans terminated with polylactosamine extensions were also detected at low levels. A subset of the N-glycans linked to these trophoblasts were sialylated, primarily with terminal NeuAcα2-3Gal sequences. EVT were decorated with the same N-glycans as STB and CTB, except in different proportions. The level of bisecting type N-glycans was reduced, but the level of N-glycans decorated with polylactosamine sequences were substantially elevated compared with the other types of trophoblasts. The level of triantennary and tetraantennary N-glycans was also elevated in EVT. The sialylated N-glycans derived from EVT were completely susceptible to an α2-3 specific neuraminidase (sialidase S). The possibility exists that the N-glycans associated with these different trophoblast subpopulations could act as functional groups. These potential relationships will be considered.

Highlights

From the ‡Department of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom; §Department of Gynaecology and Obstetrics, Faculty of Medicine, Geneva, Switzerland; ¶Department of Obstetrics and Gynecology, Washington University, School of Medicine, St
Extravillous cytotrophoblasts (EVT) derived from placental stem cells penetrate through the tips of the anchoring villi and differentiate into invasive trophoblasts that migrate into the decidua, myometrium and spiral arteries [3]
These cytotrophoblasts act in concert with maternal natural killer (NK) cells to remodel these arteries into flaccid conduits that support a three- to fourfold increase in the rate of maternal blood flow into the placental intervillous space at a reduced pressure compared with the maternal circulation (4 – 6)

Summary

Glycosylation of Human Trophoblasts

Interactions between villous trophoblasts and maternal immune cells would normally be expected to trigger major histocompatibility responses because of the expression of paternal human leukocyte antigens (HLA). STB and CTB do not express the HLA class I molecules that are necessary to evoke such responses [7, 8] This absence of HLA molecules on STB and CTB could make these trophoblasts potential targets for lysis by NK cells [9]. Unlike CTB and STB, EVT express on their cell surface a classical paternal HLA class Ia molecule designated HLA-C [7, 8]. This presentation means that EVT are semiallogeneic during natural pregnancies and are potentially subject to powerful histocompatibility-based immune responses. Glycomic analysis of STB, CTB, and EVT was performed in this study to determine if the N-glycans associated with these cells have potential functional roles

EXPERIMENTAL PROCEDURES

RESULTS

DISCUSSION