Involvement of Matrix Metalloproteinases and their Inhibitors in Bovine Cystic Ovarian Disease

PERALTA B; BARAVALLE M.E. (EQUAL CONTRIBUTION); BELOTTI, E.M. (EQUAL CONTRIBUTION); STASSI A.; SALVETTI, N.R.; ORTEGA, H.H.; REY, F.; VELAZQUEZ M.M.L.

JOURNAL OF COMPARATIVE PATHOLOGY

ELSEVIER SCI LTD

Lugar: Amsterdam; Año: 2016 vol. 56 p. 191 - 201

0021-9975

The most important regulators of tissue remodelling during ovarian follicular growth, development, ovulationand atresia are gonadotropins, steroid hormones, growth factors and different proteolytic enzymes. Matrix metalloproteinases(MMPs) such as collagenase or gelatinase (i.e. MMP-1, -8, -2 and -9) and associated tissueinhibitors of metalloproteinases (TIMP-1, -2, -3 and -4) control connective tissue remodelling during follicularrupture. In this study, we hypothesized that an imbalance in theMMPeTIMP system may be an intra-ovariancomponent that contributes to the pathogenesis of cystic ovarian disease (COD) in cows. Taking into accountthat the control ofMMPactivity by TIMPs could determine their effects in both physiological and pathologicalconditions, MMP and TIMP mRNA and protein expression was examined by real-time polymerase chainreaction (RT-PCR) and immunohistochemistry (IHC), respectively, in ovaries from control cows and cowswith COD. Expression of mRNA encoding MMP-2, TIMP-1 and TIMP-2 was lower in follicular cysts thanin control pre-ovulatory follicles, while the results by IHC showed this imbalance only for TIMP-2 proteinexpression. Additional analysis by zymography to evaluate the gelatinase activity of MMP-2 and MMP-9demonstrated higher MMP-2 activity in follicular fluid (FF) of cysts than in FF of pre-ovulatory follicles.On the other hand, MMP-9 activity was increased in follicular cysts and absent in the FF of pre-ovulatoryfollicles. These findings suggest that the altered mRNA expression and activities of the MMPeTIMP systemmay be related to the failure in ovulation and follicular development observed in COD.