Composition and significance of glycosaminoglycans in the uterus and placenta of mammals

Oliveira, Gleidson Benevides de; Vale, André Menezes do; Santos, Amílton Cesar dos; Moura, Carlos Eduardo Bezerra de; Rocha, Hugo Alexandre de Oliveira; Oliveira, Moacir Franco de

doi:10.1590/S1516-8913201500281

Human and Animal Health • Braz. arch. biol. technol. 58 (4) • Jul-Aug 2015 • https://doi.org/10.1590/S1516-8913201500281 linkcopy

Composition and significance of glycosaminoglycans in the uterus and placenta of mammals

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Glycosaminoglycans (GAGs) are heteropolysaccharides in mammalian tissue and consist of repeated disaccharide units with mono-sulfated or non-sulfated monosaccharides. GAGs are important components of the Extracellular Matrix (ECM) with several physiological roles, in the recognition, migration, adhesion, proliferation and differentiation processes. They are also important in angiogenesis, blood homeostasis, immune reactions, follicule development and also in the development of pathologies such as infertility, tumors and metastases. It has been shown that the profile of glycosaminoglycans in the uterine and placental tissues is highly variable throughout the reproductive cycle and during pregnancy. It may be directly related to their physiological or pathological functions in the tissue. The latter has recently triggered special clinical interest. Current review collaborates for a deeper knowledge on the profile and importance of GAGs in uterine and placental tissues throughout the reproductive cycle and pregnancy. It also covers information on the involvement of these molecules in pathological processes.

Extracellular matrix; hormonal fluctuation; reproductive events; euterium mammals; pathology

Species	Tissue	GAGs	Physiology	Reference
Ovariectomized female rats	Uterine horns and cervix	-DS, HS and HA in both tissues; -Use of estrogen associated to DS increase; -Treatment with progestagen: reduction of HS in the horns and increase of HS in the cervix; -Use of estrogen + progesterone: increase of sulfated GAGs.	-Modulated by sexual hormones;	Kofoed et al. (1972, 1977); Simões et al. (2012).
Female rats	Uterine horns	HA: increase when the implantation of the embryo occurs. Other GAGs remain constant during the first five days of pregnancy.	HA: biosynthesis followed by decidual response in the endometrium and may enhance the implantation of the embryo.	Carson et al. (1987)
Female rats	Cervix	- GAGs: DS, HS and HA; - Greater amount of GAGs in the estrus phase; - DS predominant in estrus and HS in the proestrus.	Hormonal variation related to the estrus may affect the uterine cervix through the effect in the production of sulfate heparan and sulfate dermatan.	Cubas et al. (2010)
Female mices	Cervix (pregnancy)	Relaxin (-/-) mice: lower Has2 and Aquaporin3 expression on day 18.5 of pregnancy and decreased cervical HA compared with wild-type Relaxin (+/+). Relaxin (-/-) mice treated with relaxin: Chronic infusion of relaxin for 4 or 6 days reversed these phenotypes and increased Has2 and Aquaporin3.	Relaxin alters aquaporin expression in the cervix and initiates changes in GAGs composition through increased HA synthesis. These actions of relaxin collectively promote water recruitment into the extracellular matrix to loosen the dense collagen fiber network.	Soh et al. (2012)
Female albino rats	Cervix (pregnancy)	Intracervical infusion of hyaluronidase: a significant reduction of CS/DS and HS. Reduction in HA staining in the lamina propria and the area surrounding the blood vessels.	Intracervical hyaluronidase infusion promoted a significant reduction in the concentration of sulfated GAGs.	Souza et al. (2014)
Female rats and women	Cervix (pregnancy at term)	HA: biosynthesis increase close to birth, with peak on day of birth.	Increase due to RNAm HAS2 transcription close to birth, suggesting HÁ regulation in the cervix.	Straach et al. (2005)
Female rabbit	Uterus	Predominance of HS, followed by DS, HA and CS.	Difference in GAGs composition between the uterine layers suggest that the later have different roles in reproduction.	Endo and Yosizawa (1975)
Female rabbit	Myometrium from ovariectomized females	CS: predominant followed by DS, HS and HA and a small amount of glycoprotein acids.		Endo et al. (1978)
Female rabbit	Uterus treated with estrogen	Main GAGs: CS, HS and DS	Treatment with estrogen increases the synthesis of sulfated GAGs in the uterus, resulting from the proliferation of the later due to hormone activity.	Munakata et al. (1984)
Women	Endometrium Cervix (pregnancy)	Predominance of CS. DS and HS in smaller amounts. The collagen and sulfated gags were elevated in tissue.	During the menstrual cycle, GAGs would be involved in the growth and remodeling of the endometrium.	Nasciutti et al. (2006) Myers et al. (2008)

Species	Tissue	GAGs	Physiology	Reference
Human	Placenta at term	-Hyaluronic acid, Chondroitin 6 sulfate, Chondroitin 4 sulfate. -Small portion of DS and HS between the maternal and fetal interface.	DS and HS form na electrochemical barrier against the passage of immunocompetent cells from the mother to the fetus.	Calatroni and Di Ferrante (1969).
Human	Young placenta Placenta at term	-Young placenta: CS and non-sulfated chondroitin in great amounts. -Placenta at term: greater amounts of sulfated GAGs, followed by DS and HS increase.	Changes at GAGs levels with the maturation of the placenta would be related to the role of these molecules in the regulation of placenta transport.	Lee et al. (1973)
Human	-Placenta during the first 3 months -Placenta at term	-Main GAGs: CS and HA in the placenta stroma and DS and HS associated with fetal blood vessels and syncytial surface.	Maintenance of structural integrity and possibly in the blood homeostasis process.	Wasserman et al. (1983)
Human	Placenta as from pre-eclampsia	Significant difference in GAGs sulfatation pattern.	Possible bond between pre-eclampsia and changes in placental GAGs.	Warda et al. (2008)
Human	Placenta during the last 3 months	Fetal Growth Restriction (FGR): biglycan mRNA and biglycan protein expression was decreased in FGR placentae compared with control placentae. The biglycan was detected in endothelial cells and sub-endothelial cells of the perivascular region of fetal capillaries.	Reduced biglycan expression may contribute to placental thrombosis within the fetal vasculature, and may contribute to the pathogenesis of idiopathic FGR.	Murthi et al. (2010)
Ovine	Placentoma	Hyaluronic acid predominant in the initial phases and in mid pregnancy.	Regulating mechanism of hyaluronic acid which is determinant in the process of placental maturation and in fetal growth	Ott et al.(1997)

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