Autocrine/paracrine regulation of human endometrial stromal remodeling by laminin and type IV collagen

Abstract

Abstract. The biological roles of laminin and type IV collagen in human endometrial stromal tissues were investigated by the evaluation of the expression levels in human endometrial tissues using immunohistochemistry. In addition, normal human endometrial stromal cells were cultured in vitro on laminin-or type IV collagen-coated plates and subjected to cytological analyses. Cyclic production of laminin and type IV collagen were detected and the two productions were significantly increased in late proliferative and late secretory endometrial stromal cells. Unstimulated endometrial stromal cells proliferated with specific growth structures that varied depending on the extracellular matrix component coated on the culture plates. The expression levels of integrin subunits on endometrial stromal cells were sufficiently enhanced by 8Br-cAMP treatment to mask any differences in the growth structures induced by the extracellular matrix components. 8Br-cAMP-stimulating stromal cells exhibited significant survival on laminin-coated plates, while 8Br-cAMP-deprived stromal cells, after 8Br-cAMP stimulation, showed significant survival on type IV collagen-coated plates. In conclusion, human endometrial stromal cells produce laminin and type IV collagen, and these productions are possibly regulated by ovarian estrogen and progesterone. Human endometrial stromal cells specifically bind to laminin and type IV collagen via integrins, and regulate endometrial stromal cell structures, viability and differentiation. Thus, laminin and type IV collagen may autoregulate human endometrial stromal remodeling during the menstrual cycle in an autocrine and paracrine fashion.

Local remodeling of synthetic extracellular matrix microenvironments by co-cultured endometrial epithelial and stromal cells enables long-term dynamic physiological function

“…73,74 The presence of collagen IV in the stromal layer is expected as endometrial fibroblasts, like fibroblasts from many other tissues, produce collagen IV. 53 However, collagen IV immunostaining in the stromal layer was strongly visible only in the upper region of the co-culture, near the epithelial cells, and was faint in the deeper regions of the stroma (data not shown), suggesting that collagen IV in the pericellular region of the fibroblasts may derive primarily from interactions with epithelia. In normal human endometrium, collagen IV immunostaining is localized to the basement membrane except during hormone differentiation where decidual cells (stromal fibroblasts that undergo differentiation in response to hormones) secrete basement membrane proteins locally around themselves, including collagen IV and laminin.…”

“…Matrix-binding peptides were designed to capture fibronectin ( FN-binder , 0.25 mM) produced by endometrial stromal fibroblasts throughout the cycle 49,52 and both laminin and type IV collagen basement membrane proteins ( BM-binder , 0.25 mM) that are normally produced by the epithelium during all menstrual cycle stages and locally produced and accumulated in the pericellular region of hormonally responsive fibroblasts in the stroma. 49,52,53 …”

Remodeling of the human endometrial epithelium is regulated by laminin and type IV collagen

“…These results indicate that menstrual cycledependent Fas-mediated apoptotic susceptibility of human endometrial epithelium may be regulated by ECM components in BM-like-S. Our recent study showed that laminin and COL-4 differentially regulated cell viability of normal human endometrial stromal cells (5). The Fas-stimulation of normal human endometrial stromal cells has been reported to stimulate cell viability (19) and interaction with COL-4 has been reported to protect lens epithelial cells from Fas-dependent apoptosis by stimulating the production of soluble survival factors (20).…”

“…Furthermore, abnormal expression of these ECM components in the endometrium was reported in a patient with unexplained infertility (1). We recently demonstrated that laminin and COL-4 regulated normal human endometrial stromal remodeling in an autocrine/paracrine fashion during the menstrual cycle (5). Therefore, in this study, we further investigated the effects of laminin and COL-4 on endometrial epithelial remodeling.…”

“…Laminin and type IV collagen (COL-4) are well-known major components of epithelial basement membranes in the human body and have been reported to localize in the basement membrane-like structures (BM-like-S) of human endometrial epithelium (1,2). Several studies have shown that both these ECM components are highly expressed in human endometrial stromal cells and deciduas (3)(4)(5). Laminin has been reported to inhibit endometrial stromal differentiation (6,7), while both laminin and COL-4 have been found to regulate trophoblast proliferation and differentiation during pregnancy (8)(9)(10)(11).…”