Hyaluronan involvement in the changes of mouse interpubic tissue during late pregnancy and post‐partum

Abstract

The present work quantifies hyaluronan (HA) during the late pregnancy and post-partum in order to provide a better understanding of the role of HA in the adaptations that occur in the pubic symphysis during this period. HA was quantified in situ (histochemically) and in interpubic tissue extracts by fluorimetric assay. Samples were taken from virgin mice and from pregnant animals at various stages of pregnancy: 12th-18th days into pregnancy, the day of delivery (D19) and the 3rd and 5th day post-partum. The quantitative fluorimetric analysis indicated a gradual increase of HA in the interpubic tissue throughout late pregnancy (2.4-14.6 microg/mg dry weight). This was followed by a decrease beginning on D19 (12.4 microg/mg), reaching close to virgin levels (2.2 microg/mg) on the 5th day post-partum. The same optical density changes could be seen in the HA staining. Furthermore, the histochemical analysis demonstrated the presence of HA both in the extracellular matrix of the tissue and within its cells. Such results indicate that the extracellular presence of HA may contribute to the transformation of the symphysis into a flexible structure. In addition, HA's intracellular presence (until the 18th day of pregnancy) may contribute to cellular proliferation. Finally, during parturition and on the 5th day post-partum, HA may contribute to the maintenance of the myofibroblastic phenotype of ligament cells, aiding the ligament involution after parturition.

Changes of Large Molecular Weight Hyaluronan and Versican in the Mouse Pubic Symphysis Through Pregnancy1

“…This matrix is abundant in HA and the CS/DS-containing proteoglycans versican and decorin. While an increase in HA has previously been reported in the term pregnant IpL [17], the current study enhances our understanding by providing quantitative assessment of all GAGs in the PS including HA; determines the relative proportion of HA to CS/DS through pregnancy; elucidates HA size, which impacts its function; and identifies the HA synthase isozymes regulated in the IpL. Furthermore, we provide evidence that maximal expansion and flexibility of the IpL at the time of labor is not achieved by loss of total collagen, change in the relative ratio of fibril collagens I, II, and III, or changes in C-terminal processing of collagen I.…”

“…Ultrastructural and immunohistochemical studies suggest that rearrangement of collagen and elastic fibers and changes in proteoglycan and hyaluronan (HA) composition at term are important in PS remodeling [16][17][18][19][20][21]. In addition, proteolytic enzymes such as matrix metalloprotease 2 and cathepsin K and B and tissue inhibitors of metalloproteases (TIMP1 and TIMP2) are proposed to contribute to symphysis relaxation [9,16,[21][22][23].…”

Evidence of macrophage modulation in the mouse pubic symphysis remodeling during the end of first pregnancy and postpartum

“…Our double immunofluorescent results showed that IpL F4/80 + cell co-localize mainly with versican at the end of pregnancy and with HA, versican and decorin at postpartum. Although the presence and content of these three ECM components are well characterized in mouse interpubic tissues during pregnancy and postpartum www.nature.com/scientificreports/ remodeling 8,11,17 , this is, to our knowledge, the first description of their association with F4/80 + cells. Although a small amount of pro-inflammatory low molecular weight (MW) HA had been previously registered in IpL at the end of pregnancy 8 , apparently no co-localization between F4/80 + cells and HA was observed in our confocal results from D18 to D19.…”

Time-dependent regulation of morphological changes and cartilage differentiation markers in the mouse pubic symphysis during pregnancy and postpartum recovery

“…Similar to in vitro mesenchymal cells in 3D culture, in vivo enthesis development after birth and to the repair of bone fractures [ 46 , 52 , 53 , 54 ], under compressive conditions, histological evaluation of the osteoligamentous junction and PS cell phenotypes and the localization of cartilage markers showed an apparent acceleration in the rate and extent of chondrogenesis. Conversely, at 1dpp, there were decreases in the numbers of cells testing positive for Sox9 or Col2a1 and an increase in Runx2 production by elongated cells at both IpL osteoligamentous regions when compressive forces were disturbed by changes in collagen fibre compaction and hyaluronic acid [ 27 , 28 ] and versican content [ 28 ] and the activity of MMPs, TIMPs and cathepsins [ 22 , 24 ]. Similar to results described during embryonic mouse endochondral ossification [ 40 ], these changes in Sox9 and Runx2 expression pattern at 1dpp in IpL osteoligamentous cells can also indicate that Sox9 is dominant over Runx2 function in terms of osteochondral progenitors that are destined for a chondrogenic lineage during PS remodelling.…”