Abstract
BackgroundRemodeling of the extracellular matrix is one of the most striking features observed in the uterus during the estrous cycle and after hormone replacement. Versican (VER) is a hyaluronan-binding proteoglycan that undergoes RNA alternative splicing, generating four distinct isoforms. This study analyzed the synthesis and distribution of VER in mouse uterine tissues during the estrous cycle, in ovariectomized (OVX) animals and after 17beta-estradiol (E2) and medroxyprogesterone (MPA) treatments, either alone or in combination.MethodsUteri from mice in all phases of the estrous cycle, and animals subjected to ovariectomy and hormone replacement were collected for immunoperoxidase staining for versican, as well as PCR and quantitative Real Time PCR.ResultsIn diestrus and proestrus, VER was exclusively expressed in the endometrial stroma. In estrus and metaestrus, VER was present in both endometrial stroma and myometrium. In OVX mice, VER immunoreaction was abolished in all uterine tissues. VER expression was restored by E2, MPA and E2+MPA treatments. Real Time PCR analysis showed that VER expression increases considerably in the MPA-treated group. Analysis of mRNA identified isoforms V0, V1 and V3 in the mouse uterus.ConclusionThese results show that the expression of versican in uterine tissues is modulated by ovarian steroid hormones, in a tissue-specific manner. VER is induced in the myometrium exclusively by E2, whereas MPA induces VER deposition only in the endometrial stroma.
Highlights
Remodeling of the extracellular matrix is one of the most striking features observed in the uterus during the estrous cycle and after hormone replacement
Salgado et al [17] have shown the differential distribution of four members of the small leucine-rich proteoglycan (SLRP) family in mouse endometrium and myometrium during the estrous cycle, suggesting that their expression in the uterine ECM is modulated by ovarian hormones
In the E2+MPA-treated group, VER was present as a network of thin filaments in the ECM in the whole endometrial stroma, except at the interface between the deep stroma and the myometrium of the antimesometrial region
Summary
Remodeling of the extracellular matrix is one of the most striking features observed in the uterus during the estrous cycle and after hormone replacement. This study analyzed the synthesis and distribution of VER in mouse uterine tissues during the estrous cycle, in ovariectomized (OVX) animals and after 17beta-estradiol (E2) and medroxyprogesterone (MPA) treatments, either alone or in combination. Estrogen (E2) produced during estrus stimulates epithelial cell proliferation and synthesis of progesterone receptors (PR). Salgado et al [17] have shown the differential distribution of four members of the small leucine-rich proteoglycan (SLRP) family in mouse endometrium and myometrium during the estrous cycle, suggesting that their expression in the uterine ECM is modulated by ovarian hormones. HA disappeared from the decidual region immediately surrounding the implantation chamber, whereas VER accumulated in the same region, suggesting this proteoglycan plays a role in proliferation and differentiation of endometrial fibroblasts into decidual cells, and may influence trophoblast invasion
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