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

• Published in: Human reproduction update 2024-01, Vol.30 (1), p.81-108
• Main Authors: 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, Chiu, Philip C N
• Format: Article
• Language: English
• Subjects: Abortion, Spontaneous; Female; Glycosylation; Glycosyltransferases - metabolism; Humans; Placenta - metabolism; Polysaccharides - metabolism; Pregnancy; Trophoblasts - metabolism
• ISSN: 1355-4786; 1460-2369; 1460-2369
• DOI: 10.1093/humupd/dmad024

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–fe