Targeting Aberrantly Elevated Sialyl Lewis A as a Potential Therapy for Impaired Endometrial Selection Ability in Unexplained Recurrent Miscarriage

Ma, Zhi; Yang, Huixia; Kessler, Mirjana; Sperandio, Markus; Mahner, Sven; Jeschke, Udo; Schönfeldt, Viktoria von

doi:10.3389/fimmu.2022.919193

Cited by 3 publications

(3 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The assays were conducted as described before [18]. Briefly, endometrial RL95-2 cells were firstly plated into a T25 flask containing 20 ng/ml recombinant human IL-1β (Cat#201-LB, R&D Systems, USA) for 48 h to acquire adequate cells for preparing the in vitro endometrial monolayer.…”

Section: Il-1β Treatmentmentioning

confidence: 99%

“…The in vitro implantation was performed in 8-well chamber slides, and RL95-2 cells monolayers preparation was as above mentioned. Spheroids of HTR-8/SVneo cells were generated as previously described [18]. Briefly, 2 × 10 4 cells per 30 μL medium drop were added onto the inverted lid over Petri dishes filled with 5 ml DPBS.…”

Section: In Vitro Implantation Assaymentioning

confidence: 99%

“…Recently, we demonstrated that two other Lewis epitopes sLeA and LeX were upregulated in the decidual cells of patients with unexplained recurrent miscarriage (uRM). More specifically, sLeA was further demonstrated to be a potential target against abnormal implantation in uRM [18]. Lewis antigens synthesis is a process of stepwise addition of sialic acid and fucose residues via the action of specific ST3 beta-galactoside alpha-2,3-sialyltransferases (ST3GALs) and fucosyltransferases (FUTs) [19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Sialyl Lewis X mediates interleukin-1 beta-induced trophoblast adhesion to endometrial cells during human embryo implantation

Kessler

Chelariu-Raicu

et al. 2023

Biology of Reproduction

Self Cite

View full text Add to dashboard Cite

Cell surface carbohydrate antigens sialyl Lewis X (sLeX) and Lewis Y (LeY) are paramount glycoconjugates and are abundantly expressed in the receptive endometrium. Furthermore, among the important biological functions of both antigens is their role in leukocytes adhesion and extravasation. Interleukin-1 beta (IL-1β) is involved in the process of human embryo implantation and placenta development. Here we used an in vitro model to investigate whether sLeX and LeY are playing a role in the embryo implantation process mediated by IL-1β. Our results are showing that the expression of cell surface sLeX was enhanced in endometrial RL95-2 cells after exposure to IL-1β. RT-qPCR detection indicated that the transcript level of glycosyltransferase gene Fucosyltransferase 3 (FUT3) was significantly elevated and that of FUT4/7 and ST3 beta-galactoside alpha-2,3-sialyltransferase 3/4 (ST3GAL3/4) were decreased by treatment with IL-1β. Modulatory role of glycosyltransferase FUT3 on sLeX biosynthesis was determined by FUT3 siRNA transfection in RL95-2 cells. Results showed that the expression level of sLeX was suppressed, but no change was observed in regard to LeY. Moreover, IL-1β promoted the HTR-8/SVneo trophoblast spheroids attachment to the RL95-2 endometrial monolayer, which was partially blocked by anti-sLeX antibody and FUT3 knockdown. Gene expression analysis of the RNA-seq transcriptome data from human secretory endometrium demonstrated a significantly higher level of FUT3 in the mid-secretory phase compared to the early secretory phase, which was correlated with the expression of IL1B. In summary, the inflammatory microenvironment at the fetomaternal interface can regulate the glycosylation pattern of endometrial cells at the time of implantation. SLeX can be significantly induced by IL-1β via increasing FUT3 expression, which facilitates the trophoblast adhesion during embryo implantation.

show abstract

Section: Il-1β Treatmentmentioning

confidence: 99%

Section: In Vitro Implantation Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sialyl Lewis X mediates interleukin-1 beta-induced trophoblast adhesion to endometrial cells during human embryo implantation

Kessler

Chelariu-Raicu

et al. 2023

Biology of Reproduction

Self Cite

View full text Add to dashboard Cite

show abstract

Decreased B7-H3 promotes unexplained recurrent miscarriage via RhoA/ROCK2 signaling pathway and regulates the secretion of decidual NK cells

Zhang

Ding

et al. 2022

Biology of Reproduction

View full text Add to dashboard Cite

The cause for at least 50% of recurrent miscarriages (RM) is unclear, defined as unexplained recurrent miscarriages (uRM). B7-H1 (PD-L1), a molecule of the B7 family, promotes tumor development by modulating immune evasion, and recent researchers have also attached importance to the role of B7-H3, another molecule of B7 family, in tumor. Based on the similarity between growth and immune response in tumors and pregnancy, we first explored the role of B7-H3 in uRM. We found reduced levels of B7-H3 in villus tissue of uRM patients, and it was mainly expressed on the cell membrane of extravillous trophoblasts (EVT). Further, the HTR-8/SVneo and JEG-3 cells were selected to explore the role of B7-H3 in proliferation, apoptosis, tube formation, migration, and invasion. We found that B7-H3 regulated trophoblast migration and invasion via RhoA/ROCK2 signaling pathway. Inflammatory cytokines were detected through ELISA after co-culturing with decidual natural killer cells (dNK) and B7-H3-knockout JEG-3. Results showed that B7-H3 inhibited IL-8 and IP-10 secretion from dNK. In a CBA/J × DBA/2 abortion-prone mice model, treatment with B7-H3-Fc protein successfully reduced the rate of embryo resorption. In conclusion, our results revealed a possible mechanism by which decreased B7-H3 on trophoblasts of uRM inhibited trophoblast migration and invasion and increased IL-8 and IP-10 secretion from dNK. Furthermore, B7-H3 may be a promising new therapeutic target in uRM patients.

show abstract

The functional roles of protein glycosylation in human maternal–fetal crosstalk

Zhong,

Li,

Burton

et al. 2023

Human Reproduction Update

View full text Add to dashboard Cite

BACKGROUND The establishment of maternal–fetal crosstalk is vital to a successful pregnancy. Glycosylation is a post-translational modification in which glycans (monosaccharide chains) are attached to an organic molecule. Glycans are involved in many physiological and pathological processes. Human endometrial epithelium, endometrial gland secretions, decidual immune cells, and trophoblasts are highly enriched with glycoconjugates and glycan-binding molecules important for a healthy pregnancy. Aberrant glycosylation in the placenta and uterus has been linked to repeated implantation failure and various pregnancy complications, but there is no recent review summarizing the functional roles of glycosylation at the maternal–fetal interface and their associations with pathological processes. OBJECTIVE AND RATIONALE This review aims to summarize recent findings on glycosylation, glycosyltransferases, and glycan-binding receptors at the maternal–fetal interface, and their involvement in regulating the biology and pathological conditions associated with endometrial receptivity, placentation and maternal–fetal immunotolerance. Current knowledge limitations and future insights into the study of glycobiology in reproduction are discussed. SEARCH METHODS A comprehensive PubMed search was conducted using the following keywords: glycosylation, glycosyltransferases, glycan-binding proteins, endometrium, trophoblasts, maternal–fetal immunotolerance, siglec, selectin, galectin, repeated implantation failure, early pregnancy loss, recurrent pregnancy loss, preeclampsia, and fetal growth restriction. Relevant reports published between 1980 and 2023 and studies related to these reports were retrieved and reviewed. Only publications written in English were included. OUTCOMES The application of ultrasensitive mass spectrometry tools and lectin-based glycan profiling has enabled characterization of glycans present at the maternal–fetal interface and in maternal serum. The endometrial luminal epithelium is covered with highly glycosylated mucin that regulates blastocyst adhesion during implantation. In the placenta, fucose and sialic acid residues are abundantly presented on the villous membrane and are essential for proper placentation and establishment of maternal–fetal immunotolerance. Glycan-binding receptors, including selectins, sialic-acid-binding immunoglobulin-like lectins (siglecs) and galectins, also modulate implantation, trophoblast functions and maternal–fetal immunotolerance. Aberrant glycosylation is associated with repeated implantation failure, early pregnancy loss and various pregnancy complications. The current limitation in the field is that most glycobiological research relies on association studies, with few studies revealing the specific functions of glycans. Technological advancements in analytic, synthetic and functional glycobiology have laid the groundwork for further exploration of glycans in reproductive biology under both physiological and pathological conditions. WIDER IMPLICATIONS A deep understanding of the functions of glycan structures would provide insights into the molecular mechanisms underlying their involvement in the physiological and pathological regulation of early pregnancy. Glycans may also potentially serve as novel early predictive markers and therapeutic targets for repeated implantation failure, pregnancy loss, and other pregnancy complications.

show abstract

Targeting Aberrantly Elevated Sialyl Lewis A as a Potential Therapy for Impaired Endometrial Selection Ability in Unexplained Recurrent Miscarriage

Cited by 3 publications

References 53 publications

Sialyl Lewis X mediates interleukin-1 beta-induced trophoblast adhesion to endometrial cells during human embryo implantation

Sialyl Lewis X mediates interleukin-1 beta-induced trophoblast adhesion to endometrial cells during human embryo implantation

Decreased B7-H3 promotes unexplained recurrent miscarriage via RhoA/ROCK2 signaling pathway and regulates the secretion of decidual NK cells

The functional roles of protein glycosylation in human maternal–fetal crosstalk

Contact Info

Product

Resources

About