Collagen type IV at the fetal–maternal interface

Abstract

IntroductionExtracellular matrix proteins play a crucial role in influencing the invasion of trophoblast cells. However the role of collagens and collagen type IV (col-IV) in particular at the implantation site is not clear.MethodsImmunohistochemistry was used to determine the distribution of collagen types I, III, IV and VI in endometrium and decidua during the menstrual cycle and the first trimester of pregnancy. Expression of col-IV alpha chains during the reproductive cycle was determined by qPCR and protein localisation by immunohistochemistry. The structure of col-IV in placenta was examined using transmission electron microscopy. Finally, the expression of col-IV alpha chain NC1 domains and collagen receptors was localised by immunohistochemistry.ResultsCol-IV alpha chains were selectively up-regulated during the menstrual cycle and decidualisation. Primary extravillous trophoblast cells express collagen receptors and secrete col-IV in vitro and in vivo, resulting in the increased levels found in decidua basalis compared to decidua parietalis. A novel expression pattern of col-IV in the mesenchyme of placental villi, as a three-dimensional network, was found. NC1 domains of col-IV alpha chains are known to regulate tumour cell migration and the selective expression of these domains in decidua basalis compared to decidua parietalis was determined.DiscussionCol-IV is expressed as novel forms in the placenta. These findings suggest that col-IV not only represents a structural protein providing tissue integrity but also influences the invasive behaviour of trophoblast cells at the implantation site.

Tuning trophoblast invasion in a gelatin hydrogel via soluble cues from the maternal-fetal interface

“…Gelatin is denatured collagen and hence retains cell binding motifs and degradation sites that allow for cell attachment and matrix remodeling, key processes relevant to invasion (23,27,(30)(31)(32). The endometrium contains collagens I, III, IV, V, and VI, rendering gelatin relevant in terms of its extracellular matrix composition (33,34) Unlike traditional two-dimensional wound healing assays or Boyden chamber assays, spheroid invasion assays in biomaterial platforms can replicate the three-dimensional structure of an invading blastocyst and provide a matrix through which cells can invade. We demonstrate reproducible spheroid formation using the HTR-8/SVneo cell line, resulting in spheroid size within the range of an invading blastocyst (28).…”

The Placenta as an Organ and a Source of Stem Cells and Extracellular Matrix: A Review

“…During decidualization (i.e. dramatic endometrial remodeling after ovulation in preparation for pregnancy) matricellular proteins (basement membrane) found around individual decidual cells are comprised of laminin α1, α2, β1, β2 and γ1 chains, fibronectin, type IV collagen and heparin sulfate proteoglycan [Wewer et al, 1985;Korhonen and Virtanen, 1997;Gellersen et al, 2007;Oefner et al, 2015]. Decidualizing stromal cells control trophoblast invasion, suppress inflammation and oxidative stresses, and desensitize maternal immune responses [Gellersen et al, 2007].…”

Extracellular matrix in epitheliochorial, endotheliochorial and haemochorial placentation and its potential application for regenerative medicine

“…The ECM is composed of supramolecular glycoproteins (Bornstein & Sage, ; Hynes, ; Mouw, Ou, & Weaver, ; Oefner et al., ; Ricard‐Blum, ). The interstitial matrix forms loose networks of collagen fibres, varying in density because of the presence of other proteins (Hallmann et al., ).…”

“…The interstitial matrix forms loose networks of collagen fibres, varying in density because of the presence of other proteins (Hallmann et al., ). The major components include the following: (i) polysaccharides of the glycosaminoglycan and proteoglycans lines (are composed of polysaccharides but too of proteins) such as aggrecan, veriscan, fibromodulin, biglycan and lumican (Figure ), (ii) Structure proteins, with special reference to collagens, are subdivided into fibrillar collagens of types I, II, III, V and XI; non‐fibrillar collagens of types VI, VIII, IX, XII and XIV; network collagen types IV, VIII and X as well as membrane collagens of types XIII, XVII and XXV (Oefner et al., ; Ricard‐Blum, ), (iii) adhesive collagen glycoproteins, for example fibronectin, tenascin, elastin, laminin and vitronectin (Hynes, ; Ricard‐Blum, ; Sati et al., ), and (iv) non‐structural matri‐ or pericellular proteins that perform multiple interactions with structural proteins, cell receptors, proteases, hormones and other bioactive molecules (Oefner et al., ). In addition, the basement membrane acts as a dense, sheet‐like network to separate cell components and is built by four groups of glycoproteins: laminins, collagen type IV, heparin sulfate proteoglycans and nidogens (Hallmann et al., ; Kadler, Hill, & Canty‐Laird, ; Mouw et al., ).…”