Functional glycosylation in the human and mammalian uterus

Abstract

BackgroundGlycosylation is the most common and structurally diverse of all the post-translational modifications of proteins. Lipids and extracellular matrices are also often glycosylated. The mammalian uterus is highly enriched in glycoconjugates that are associated with the apical surfaces of epithelial cells and the secretions released by both epithelial and stromal cells. These glycoconjugates interact primarily with sperm, the implanting embryo, the fetus, and any pathogen that happens to gain entry into the uterus. Secretions of the endometrial glands increase substantially during the luteal phase of the menstrual cycle. These secretions are highly enriched in glycoproteins and mucins that promote specific uterine functions.FindingsLectins and antibodies have been employed in the majority of the studies focused on uterine glycosylation have employed to define the expression of carbohydrate sequences. However, while these studies provide insight about potential glycosylation, precise information about glycan structure is lacking. Direct sequencing studies that employ biochemical or mass spectrometric methods are far more definitive, but have rarely been employed with uterine glycoproteins. Both lectin/antibody binding and direct carbohydrate sequencing studies that have been focused on the mammalian uterus are reviewed. The primary functional role of the eutherian uterus is to facilitate fertilization and nurture the developing embryo/fetus. Trophoblasts are the primary cells that mediate the binding of the embryo and placenta to the uterine lining. In mammals that utilize hemochorial placentation, they invade the decidua, the specialized endometrial lining that forms during pregnancy. Trophoblasts have also been analyzed for their lectin/antibody binding as a complement to the analysis of the uterine cells and tissues. They will also be reviewed here.ConclusionsThe functional roles of the glycans linked to uterine and trophoblast glycoconjugates remain enigmatic. Another major question in the human is whether defects in placental or uterine glycosylation play a role in the development the Great Obstetrical Syndromes. More recent findings indicate that changes in glycosylation occur in trophoblasts obtained from patients that develop preeclampsia and preterm birth. The functional significance of these changes remain to be defined. Whether such shifts happen during the development of other types of obstetrical syndromes remains to be determined.

Patterns of protein glycosylation in bovine placentomes as a function of gestational age and in retained versus non‐retained placenta

“…The dynamics of this process was partly described here thanks to the analysis of samples collected during pregnancy. In the review of Clark (Clark, ), glycosylation processes in human and mammalian uterus were described. There are some reports about mouse, dog or monkey but scarce data on cows.…”

“…Lectin blotting is a good tool for searching for sugar moieties in tissues (Clark, ). Depending on lectin type, different kinds of glycosidic linkage can be determined.…”

Prenatal development in Lagostomus maximus (Rodentia, Chinchillidae): A unique case among eutherian mammals of physiological embryonic death

“…Furthermore, this expression did not differ from that observed in non‐pregnant females (Acuña et al, 2020). Uterine glycoconjugates are not only found in cells but also in secretions (Clark, 2015). The histotroph is a heterogeneous nutritional secretion (ions and molecules) secreted by the uterine glands, with multiple roles during early gestation.…”

Altered glycosylation of glycodelin in endometrial carcinoma

“…After establishing, by glycan-analyses and lectin-binding studies, that HEC-1B endometrial carcinoma cells produce glycodelin with different N-glycans than normal endometrium, we studied whether this can be seen also in endometrial carcinoma tissues. This is feasible as glycosylation of endometrial proteins is not only dependent on the phase of the menstrual cycle and menopausal status, but is further changed in malignant endometrium [48]. First, we studied glycodelin expression in normal endometrium and endometrial carcinoma.…”