Spatio-temporal expression profile of matrix metalloproteinase (Mmp) modulators Reck and Sparc during the rat ovarian dynamics

Author(s)

Levin, Gabriel ^[1] ; Coelho, Tatiane Maldonado ^{[1, 2]} ; Nobrega, Nathali Guimaraes ^[1] ; Trombetta-Lima, Marina ^{[1, 2]} ; Sogayar, Mari Cleide ^{[1, 2]} ; Oliveira Carreira, Ana Claudia ^{[3, 1, 2]}

Affiliation

^[1] Univ Sao Paulo, Med Sch, Internal Med Dept, NUCEL Cell & Mol Therapy Ctr, Rua Pangare 100, BR-05360130 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Chem Inst, Biochem Dept, BR-05508000 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Surg, BR-05508270 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Reproductive Biology and Endocrinology; v. 16, NOV 13 2018.
• Web of Science Citations: 2

Abstract

BackgroundMatrix metalloproteinases (Mmps) and their tissue inhibitors (Timps) are widely recognized as crucial factors for extracellular matrix remodeling in the ovary and are involved in follicular growth, ovulation, luteinization, and luteolysis during the estrous cycle. Recently, several genes have been associated to the modulation of Mmps activity, including Basigin (Bsg), which induces the expression of Mmps in rat ovaries; Sparc, a TGF- modulator that is related to increased expression of Mmps in cancer; and Reck, which is associated with Mmps inhibition. However, the expression pattern of Mmp modulators in ovary dynamics is still largely uncharacterized.MethodsTo characterize the expression pattern of Mmps network members in ovary dynamics, we analyzed the spatio-temporal expression pattern of Reck and Sparc, as well as of Mmp2, Mmp9 and Mmp14 proteins, by immunohistochemistry (IHC), in pre-pubertal rat ovaries obtained from an artificial cycle induced by eCG/hCG, in the different phases of the hormone-induced estrous cycle. We also determined the gene expression profiles of Mmps (2, 9, 13 14), Timps (1, 2, 3), Sparc, Bsg, and Reck to complement this panel.ResultsIHC analysis revealed that Mmp protein expression peaks at the early stages of folliculogenesis and ovulation, decreases during ovulation-luteogenesis transition and luteogenesis, increasing again during corpus luteum maintenance and luteolysis. The protein expression patterns of these metalloproteinases and Sparc were inverse relative to the pattern displayed by Reck. We observed that the gene expression peaks of Mmps inhibitors Reck and Timp2 were closely paraleled by Mmp2 and Mmp9 suppression. The opposite was also true: increased Mmp2 and Mmp9 expression was concomitant to reduced Reck and Timp2 levels.ConclusionTherefore, our results generate a spatio-temporal expression profile panel of Mmps and their regulators, suggesting that Reck and Sparc seem to play a role during ovarian dynamics: Reck as a possible inhibitor and Sparc as an inducer of Mmps. (AU)

• FAPESP's process: 13/18842-8 - Evaluation of MMPs, TIMPs, RECK, SPARC and Bsg expression during rat ovarian dynamics
• Grantee: Gabriel Levin
• Support Opportunities: Scholarships in Brazil - Scientific Initiation