Involvement of matrix metalloproteinases and their inhibitors in bovine cystic ovarian disease

PERALTA MB; BARAVALLE ME; BELOTTI EM; STASSI AF; SALVETTI NR; ORTEGA HH; REY F; VELÁZQUEZ MML

Mar del Plata

Congreso; Reunión anual de SAIC, SAI, SAFE; 2016

The most important regulators of tissue remodellingduring ovarian follicular growth, development,ovulation and atresia are gonadotropins, steroid hormones, growth factors and different proteolytic enzymes.Matrix metalloproteinases such as collagenase or gelatinase (MMP-1, -8, -2, -9) and associatedtissue inhibitors of metalloproteinases (TIMP-1, -2, -3 and -4) control connectivetissue remodelling during follicular rupture. In this study, we hypothesized that an imbalance inthe MMPs/TIMPs system may be an intraovariancomponent that contributes to the pathogenesis of cystic ovarian disease (COD) in cows. Taking into account that thecontrol of MMP activity by TIMPs could determine theireffects in both physiological and pathological conditions, MMP mRNA and protein expression was examined by real time PCRand immunohistochemistry, respectively, in ovaries from control cows and cowswith COD. mRNA levels of MMP-2, TIMP-1 and TIMP-2 were lower in follicularcysts than in control preovulatory follicles, while the results by immunohistochemistry showedthis imbalance only for TIMP-2 protein expression.Additional analysis by zymography to evaluate the gelatinase activity of MMP-2and MMP-9 demonstrated higher MMP-2 activity in follicular fluid (FF) of cyststhan in FF of preovulatory follicles. On the other hand,MMP-9 activity was increased in follicular cysts and absent in FF of preovulatoryfollicles. These findings suggest that the altered mRNA and protein expression of the MMP/TIMPsystem and enzymatic activity for MMP-9 may be related to the failure in ovulation and follicular development observed inCOD.