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8. Adrenomedullin has a pivotal role in trophoblast differentiation: A promising nanotechnology-based therapeutic target for early-onset preeclampsia

Author

Zhang, Qingqing, primary, Lee, Cheuk-Lun, additional, Yang, Tingyu, additional, Li, Jianlin, additional, Zeng, Qunxiong, additional, Liu, Xiaofeng, additional, Liu, Zhongzhen, additional, Ruan, Degong, additional, Li, Zhuoxuan, additional, Kan, Anita S. Y., additional, Cheung, Ka-Wang, additional, Mak, Annisa S. L., additional, Ng, Vivian W. Y., additional, Zhao, Huashan, additional, Fan, Xiujun, additional, Duan, Yong-Gang, additional, Zhong, Liuying, additional, Chen, Min, additional, Du, Meirong, additional, Li, Raymond H. W., additional, Liu, Pengtao, additional, Ng, Ernest H. Y., additional, Yeung, William S. B., additional, Gao, Ya, additional, Yao, Yuanqing, additional, and Chiu, Philip C. N., additional

Published
2023
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11. The functional roles of protein glycosylation in human maternal–fetal crosstalk.

Author

Zhong, Jiangming, Li, Jianlin, Burton, Graham J, Koistinen, Hannu, Cheung, Ka Wang, Ng, Ernest H Y, Yao, Yuanqing, Yeung, William S B, Lee, Cheuk-Lun, and Chiu, Philip C N

Subjects
GLYCANS, PREGNANCY complications, MISCARRIAGE, RECURRENT miscarriage, EMBRYO implantation, GLYCOSYLATION
Abstract

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. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Altered glycosylation of glycodelin in endometrial carcinoma

Author

Hautala, Laura C., Pang, Poh-Choo, Antonopoulos, Aristotelis, Pasanen, Annukka, Lee, Cheuk-Lun, Chiu, Philip C. N., Yeung, William S. B., Loukovaara, Mikko, Bützow, Ralf, Haslam, Stuart M., Dell, Anne, and Koistinen, Hannu

Abstract

Glycodelin is a major glycoprotein expressed in reproductive tissues, like secretory and decidualized endometrium. It has several reproduction related functions that are dependent on specific glycosylation, but it has also been found to drive differentiation of endometrial carcinoma cells toward a less malignant phenotype. Here we aimed to elucidate whether the glycosylation and function of glycodelin is altered in endometrial carcinoma as compared with a normal endometrium. We carried out glycan structure analysis of glycodelin expressed in HEC-1B human endometrial carcinoma cells (HEC-1B Gd) by mass spectrometry glycomics strategies. Glycans of HEC-1B Gd were found to comprise a typical mixture of high-mannose, hybrid, and complex-type N-glycans, often containing undecorated LacNAc (Galβ1–4GlcNAc) antennae. However, several differences, as compared with previously reported glycan structures of normal human decidualized endometrium-derived glycodelin isoform, glycodelin-A (GdA), were also found. These included a lower level of sialylation and more abundant poly-LacNAc antennae, some of which are fucosylated. This allowed us to select lectins that showed different binding to these classes of glycodelin. Despite the differences in glycosylation between HEC-1B Gd and GdA, both showed similar inhibitory activity on trophoblast cell invasion and peripheral blood mononuclear cell proliferation. For the detection of cancer associated glycodelin, we established a novel in situ proximity-ligation based histochemical staining method using a specific glycodelin antibody and UEAI lectin. We found that the UEAI reactive glycodelin was abundant in endometrial carcinoma, but virtually absent in normal endometrial tissue even when glycodelin was strongly expressed. In conclusion, we established a histochemical staining method for the detection of endometrial carcinoma-associated glycodelin and showed that this specific glycodelin is exclusively expressed in cancer, not in normal endometrium. Similar methods can be used for studies of other glycoproteins.

Published
2024
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20. Placenta exosomal miRNA-30d-5p facilitates decidual macrophage polarization by targeting HDAC9

Author

Bai, Kunfeng, primary, Li, Jianlin, additional, Lin, Leqian, additional, Zhang, Qingqing, additional, Zhong, Jiangming, additional, Liu, Xiaofeng, additional, Cao, Dandan, additional, Duan, Yong-Gang, additional, Yao, Yuanqing, additional, Li, Raymond H W, additional, Cheung, Ka-Wang, additional, Yeung, William S B, additional, Chiu, Philip C N, additional, and Lee, Cheuk-Lun, additional

Published
2023
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21. Transcriptomic analysis of mid‐secretory endometrium reveals essential immune factors associated with pregnancy after single euploid blastocyst transfer

Author

Cheng, Yanfei, primary, Wang, Hui, additional, Shang, Jin, additional, Wang, Jue, additional, Yin, Jingwen, additional, Zhang, Jinning, additional, Guo, Xinmeng, additional, Wang, Sidong, additional, Duan, Yong‐Gang, additional, Lee, Cheuk‐Lun, additional, Chiu, Philip C. N., additional, Zhang, Jian, additional, Yeung, William S. B., additional, Cao, Dandan, additional, and Yao, Yuanqing, additional

Published
2022
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22. Resolving the gene expression maps of human first-trimester chorionic villi with spatial transcriptome

Author

Liu, Zhongzhen, primary, Zhai, Man, additional, Zhang, Qingqing, additional, Yang, Tingyu, additional, Wan, Zunmin, additional, Li, Jianlin, additional, Liu, Xiaofeng, additional, Xu, Bo, additional, Du, Libei, additional, Chan, Rachel W. S., additional, Zhang, Li, additional, Yeung, William S. B., additional, Cheung, Ka Wang, additional, Chiu, Philip C. N., additional, Wang, Wen-Jing, additional, Lee, Cheuk-Lun, additional, and Gao, Ya, additional

Published
2022
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23. Human Early Syncytiotrophoblasts Are Highly Susceptible to SARS-CoV-2 Infection

Author

Ruan, Degong, primary, Ye, Zi-Wei, additional, Yuan, Shuofeng, additional, Li, Zhuoxuan, additional, Zhang, Weiyu, additional, Ong, Chon Phin, additional, Tang, Kaiming, additional, Guo, Jilong, additional, Xuan, Yiyi, additional, Tam, Timothy Theodore Ka Ki, additional, Huang, Yunying, additional, Zhang, Qingqing, additional, Lee, Cheuk-Lun, additional, Chiu, Philip C.N., additional, Liu, Fang, additional, Jin, Dong-Yan, additional, and Liu, Pentao, additional

Published
2022
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24. Dysregulation of the CD147 complex confers defective placental development: A pathogenesis of early‐onset preeclampsia

Author

Lee, Cheuk‐Lun, primary, Chen, Zhilong, additional, Zhang, Qingqing, additional, Guo, Yue, additional, Ng, Vivian W.Y., additional, Zhang, Baozhen, additional, Bai, Kunfeng, additional, Ruan, Degong, additional, Kan, Anita S.Y., additional, Cheung, Ka‐Wang, additional, Mak, Annisa S.L., additional, Yeung, William S.B., additional, Su, Rui, additional, Yang, Qing, additional, Chen, Min, additional, Du, Mei‐Rong, additional, Jian, Zhang, additional, Fan, Xiujun, additional, and Chiu, Philip C.N., additional

Published
2022
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27. Additional file 1 of Human placental exosomes induce maternal systemic immune tolerance by reprogramming circulating monocytes

Author

Bai, Kunfeng, Lee, Cheuk-Lun, Liu, Xiaofeng, Li, Jianlin, Cao, Dandan, Zhang, Li, Hu, Duanlin, Li, Hong, Hou, Yanqing, Xu, Yue, Kan, Anita S. Y., Cheung, Ka-Wang, Ng, Ernest H. Y., Yeung, William S. B., and Chiu, Philip C. N.

Abstract

Additional file 1. Supplementary research data of human placental exosomes induce maternal systemic immune tolerence by reprogramming circulating monocytes.

Published
2022
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28. Transcriptomic analysis of mid‐secretory endometrium reveals essential immune factors associated with pregnancy after single euploid blastocyst transfer.

Author

Cheng, Yanfei, Wang, Hui, Shang, Jin, Wang, Jue, Yin, Jingwen, Zhang, Jinning, Guo, Xinmeng, Wang, Sidong, Duan, Yong‐Gang, Lee, Cheuk‐Lun, Chiu, Philip C. N., Zhang, Jian, Yeung, William S. B., Cao, Dandan, and Yao, Yuanqing

Subjects
EMBRYO implantation, BLASTOCYST, REPRODUCTIVE technology, PREGNANCY outcomes, PREGNANCY
Abstract

Purpose: Implantation is a limiting factor for treatment success in assisted reproduction. Both embryonic and endometrial factors contribute to implantation. Embryonic factors have often been ignored in previous studies about the role of endometrium in implantation. In this study, we sought to identify the endometrial genes associated with negative pregnancy outcomes following the transfer of a single euploid blastocyst. Methods: Computational analyses of the transcriptomes of mid‐secretory endometria from nine pregnant and seven non‐pregnant patients in a cycle preceding the transfer of a single euploid blastocyst in a vitrified‐warmed cycle were performed. Results: Principal component analysis of two reported endometrial receptivity gene sets showed close clustering of the pregnant and non‐pregnant samples. Differential gene expression analysis and co‐expression module analysis identified 131 genes associated with the pregnancy status. The endometrial signatures identified highlight the importance of immune and metabolic regulation in pregnancy outcome. Network analysis identified 20 hub genes that could predict pregnancy outcomes with 88.9% sensitivity and 85.7% specificity. Single‐cell gene expression analysis highlighted the regulation of endometrial natural killer (NK) cells, T cells, and macrophages during embryo implantation. Immune cell abundance analysis supported the dysregulation of cytotoxic immune cells in the endometria of non‐pregnant women. Conclusions: We reported the first endometrial gene signature associated with pregnancy after elimination of embryo aneuploidy and highlighted the importance of the endometrial immune microenvironment and metabolic status in pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Published
2023
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43. Decidual glycodelin-A polarizes human monocytes into a decidual macrophage-like phenotype through Siglec-7

Author

Vijayan, Madhavi, Lee, Cheuk-Lun, Wong, Vera H. H., Wang, Xia, Bai, Kungfeng, Wu, Jian, Koistinen, Hannu, Seppälä, Markku, Lee, Kai-Fai, Yeung, William S. B., Ng, Ernest H. Y., Chiu, Philip C. N., Department of Clinical Chemistry and Hematology, HUS Abdominal Center, Department of Obstetrics and Gynecology, University of Helsinki, Helsinki University Hospital Area, HUSLAB, Department of Diagnostics and Therapeutics, and HUS Gynecology and Obstetrics

Subjects
FETAL-MATERNAL INTERFACE, BLOOD, Macrophage, GLYCOSYLATION, Trophoblast, PROTEIN, PAEP, DIFFERENTIATION, PREGNANCY, Glycodelin, Siglec, embryonic structures, Progestagen-associated endometrial protein, CELLS, Decidua, 1182 Biochemistry, cell and molecular biology, INVASIVENESS, Endocrine, INDOLEAMINE 2,3-DIOXYGENASE, GENE-EXPRESSION
Abstract

Decidual macrophages constitute 20-30% of the total leukocytes in the uterus of pregnant women, regulating the maternal immune tolerance and placenta development. Abnormal number or activities of decidual macrophages (dMs) are associated with fetal loss and pregnancy complications, such as preeclampsia. Monocytes differentiate into dMs in a decidua-specific microenvironment. Despite their important roles in pregnancy, the exact factors that regulate the differentiation into dMs remain unclear. Glycodelin-A (PAEP, hereafter referred to as GdA) is a glycoprotein that is abundantly present in the decidua, and plays an important role in fetomaternal defense and placental development. It modulates the differentiation and activity of several immune cell types residing in the decidua. In this study, we demonstrated that GdA induces the differentiation of human monocytes into dM-like phenotypes in terms of transcriptome, cell surface marker expression, secretome, and regulation of trophoblast and endothelial cell functions. We found that Sialic acid-binding Ig-like lectin 7 (Siglec-7) mediates the binding and biological actions of GdA in a sialic acid-dependent manner. We, therefore, suggest that GdA, induces the polarization of monocytes into dMs to regulate fetomatemal tolerance and placental development.

Published
2020

50. Decidual glycodelin-A polarizes human monocytes towards a decidual macrophage-like phenotype via siglec-7

Author

Vijayan, Madhavi, primary, Lee, Cheuk-Lun, additional, Wong, Vera H. H., additional, Wang, Xia, additional, Bai, Kungfeng, additional, Wu, Jian, additional, Koistinen, Hannu, additional, Seppälä, Markku, additional, Lee, Kai-Fai, additional, Yeung, William S. B., additional, Ng, Ernest H. Y., additional, and Chiu, Philip C. N., additional

Published
2020
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