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

PERALTA, M.B. ; BARAVALLE M.E; BELOTTI M; STASSI, A.F.; SALVETTI NR; ORTEGA H.H.; REY F; VELÁZQUEZ MML

Mar del Plata

Encuentro; LXI Reunión anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

Sociedad Argentina de Investigación Clínica

The most important regulators of tissue remodelling during 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 associated tissue inhibitors of metalloproteinases (TIMP-1, -2, -3 and -4) control connective tissue remodelling during follicular rupture. In this study, we hypothesized that an imbalance in the MMPs/TIMPs system may be an intraovarian component that contributes to the pathogenesis of cystic ovarian disease (COD) in cows. Taking into account that the control of MMP activity by TIMPs could determine their effects in both physiological and pathological conditions, MMP mRNA and protein expression was examined by real time PCR and immunohistochemistry, respectively, in ovaries from control cows and cows with COD. mRNA levels of MMP-2, TIMP-1 and TIMP-2 were lower in follicular cysts than in control preovulatory follicles (p < 0,05), while the results by immunohistochemistry showed this imbalance only for TIMP-2 protein expression (p < 0,05). Additional analysis by zymography to evaluate the gelatinase activity of MMP-2 and MMP-9 demonstrated higher MMP-2 activity in follicular fluid (FF) of cysts than in FF of preovulatory follicles (p < 0,05). On the other hand, MMP-9 activity was increased in follicular cysts and absent in FF of preovulatory follicles. These findings suggest that the altered mRNA and protein expression of the MMP/TIMP system and enzymatic activity for MMP-9 may be related to the failure in ovulation and follicular development observed in COD.