title: Involvement of Matrix Metalloproteinases and their Inhibitors in Bovine Cystic Ovarian Disease.
abstract: 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 (MMPs) such as collagenase or gelatinase (i.e. MMP-1, -8, -2 and -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 MMP-TIMP system may be an intra-ovarian 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 and TIMP mRNA and protein expression was examined by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC), respectively, in ovaries from control cows and cows with COD. Expression of mRNA encoding MMP-2, TIMP-1 and TIMP-2 was lower in follicular cysts than in control pre-ovulatory follicles, while the results by IHC showed this imbalance only for TIMP-2 protein expression. 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 pre-ovulatory follicles. On the other hand, MMP-9 activity was increased in follicular cysts and absent in the FF of pre-ovulatory follicles. These findings suggest that the altered mRNA expression and activities of the MMP-TIMP system may be related to the failure in ovulation and follicular development observed in COD.
authors.affiliation: Instituto de Ciencias Veterinarias del Litoral, Universidad Nacional del Litoral, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Esperanza, Santa Fe, Argentina.
authors.forename: M B
authors.initials: MB
authors.lastname: Peralta
authors.affiliation: Instituto de Ciencias Veterinarias del Litoral, Universidad Nacional del Litoral, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Esperanza, Santa Fe, Argentina.
authors.forename: M E
authors.initials: ME
authors.lastname: Baravalle
authors.affiliation: Instituto de Ciencias Veterinarias del Litoral, Universidad Nacional del Litoral, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Esperanza, Santa Fe, Argentina.
authors.forename: E M
authors.initials: EM
authors.lastname: Belotti
authors.affiliation: Instituto de Ciencias Veterinarias del Litoral, Universidad Nacional del Litoral, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Esperanza, Santa Fe, Argentina.
authors.forename: A F
authors.initials: AF
authors.lastname: Stassi
authors.affiliation: Instituto de Ciencias Veterinarias del Litoral, Universidad Nacional del Litoral, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Esperanza, Santa Fe, Argentina.
authors.forename: N R
authors.initials: NR
authors.lastname: Salvetti
authors.affiliation: Instituto de Ciencias Veterinarias del Litoral, Universidad Nacional del Litoral, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Esperanza, Santa Fe, Argentina.
authors.forename: H H
authors.initials: HH
authors.lastname: Ortega
authors.affiliation: Instituto de Ciencias Veterinarias del Litoral, Universidad Nacional del Litoral, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Esperanza, Santa Fe, Argentina.
authors.forename: F
authors.initials: F
authors.lastname: Rey
authors.affiliation: Instituto de Ciencias Veterinarias del Litoral, Universidad Nacional del Litoral, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Esperanza, Santa Fe, Argentina. Electronic address: melisavel@gmail.com.
authors.forename: M M L
authors.initials: MML
authors.lastname: Velázquez
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D002418:Cattle Diseases / Q000201:enzymology*; D005260:Female; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D010048:Ovarian Cysts / Q000662:veterinary*; D060888:Real-Time Polymerase Chain Reaction; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases
keywords: cow; matrix metalloproteinase; ovary; tissue inhibitors of metalloproteinase