Proteases of the plasminogen activator (PA) and the matrix metalloproteinase (MMP) enzyme systems are expressed in the ovulatory follicle and in the developing corpus luteum (CL). However, the functional role of these extracellular degrading protease systems in the ovulatory and CL development processes remains elusive. The first aim of this thesis was to develop a mouse model to study gonadotropin-induced CL formation. The second aim was to study the involvement of the PA and the MMP systems in gonadotropin-induced ovulation, and in CL formation and function. A mouse model for gonadotropin-induced CL formation was developed in order to control the timing of CL formation. In this model, immature mice were induced to ovulate by administrating gonadotropins and the endogenous prolactin surges were mimicked by administration of prolactin twice daily from day 2 of CL development. We observed that steroidogenic acute regulatory protein (StAR) mRNA was highly expressed at days 3 and day 6 of CL development and the levels remained high until late stages of CL regression. Since mice lacking plasminogen (plg-/-) only have a 14% reduction of ovulation efficiency, our hypothesis was that the MMP system could compensate for the loss of plasminogen. When administrating the MMP-inhibitor galardin to gonadotropin-primed ovulating mice, we found that wild-type mice (plg+/+ and C67BL/J6) and heterozygous mice (plg+/-) had an 18-20% reduction in ovulation efficiency as compared to untreated mice. Two models for CL formation, the adult pseudopregnant (psp) mouse model and a model whereby immature gonadotropin-primed mice were treated with prolactin, were used to study the formation and function of the CL in plg-/- mice treated with galardin. At day 3 of CL development, we found no alterations other than a slightly lower number of CL in plg-/- mice. This is most likely a secondary effect of the lower ovulation efficiency found in these mice. On the other hand, we found a 54% reduction in serum progesterone levels in plg-/- mice and a 37% reduction in the plg+/- mice as compared to wild type mice. At day 6 of CL development we saw a 45 % reduction of serum progesterone level in the plg-/- mice and a 22 % reduction in the plg+/- mice. A similar trend was observed at day 3 of CL development in immature gonadotropinprimed mice treated with prolactin. Galardin treatment did not alter the results significantly and the CLs were healthy and viable in these mice. In conclusion, our data suggest that both plasminogen and MMPs, alone or in combination, are dispensable for ovulation and for the formation of a viable CL under the conditions used in this study. The reduced serum progesterone levels observed in the plg-/- mice did not appear to be a result of defective CL formation. Instead, plasmin may have a novel role in the maintenance of luteal function. StAR expression may also be a good marker for CL development and regression in mice.

Lic.-avh. (sammanfattning) Umeå : University. / Härtill 3 uppsatser.

Thesis (Ph.D.)--University of Western Australia, 2003.

Thesis (Ph. D.)--University of Missouri-Columbia, 1996. / Typescript. Vita. Includes bibliographical references (leaves [109]-132. Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1996. / Typescript. Vita. Includes bibliographical references (leaves 124-142). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1996. / Typescript. Vita. Includes bibliographical references (leaves [109]-132. Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1996. / Typescript. Vita. Includes bibliographical references (leaves 124-142). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 148-171). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 148-171). Also available on the Internet.

Orientador: Joaquim Mansano Garcia / Coorientador: Naiara Saraiva Zoccal / Banca: Fábio Morato Monteiro / Banca: José Octavio Jacomini / Banca: Maria Emilia Franco Oliveira / Banca: Gilson Hélio Toniollo / Resumo: A progesterona e seus análogos têm sido utilizados para diversas finalidades na reprodução animal. O objetivo deste estudo foi avaliar a influencia da progesterona injetável no número de oócitos recuperados, na qualidade oocitária e produção embrionária de novilhas Nelore pré-púberes. Foram utilizadas 31 fêmeas com idade entre 18 a 20 meses, não gestantes e não cíclicas. As doadoras de oócitos foram divididas em 3 grupos experimentais em delineamento crossover da seguinte maneira: Grupo P0 (n=11), os animais deste grupo receberam duas aplicações de solução placebo (1 mL), com intervalo de 7 dias iniciando 14 dias (D-14) antes da primeira aspiração (D-0); Grupo P7 (n=10): os animais receberam uma aplicação de solução placebo (1 mL) 14 dias (D-14) e uma de progesterona (P4) injetável (150mg) 7 dias (D-7) antes da aspiração; Grupo P14 (n=10), neste grupo os animais receberam duas aplicações de P4 injetável (150mg) com intervalo de 7 dias, a primeira 14 dias (D-14) e a segunda 7 (D-7) dias antes da aspiração. Realizaram-se um total de três aspirações foliculares em intervalos de 28 dias. Os animais que apresentaram CL durante o experimento foram alocados em um grupo separado para serem analisados e comparados com o grupo sem CL. Os oócitos recuperados foram selecionados e submetidos aos procedimentos da PIVE. Após a confirmação da homocedasticidade (BoxCox) e normalidade (teste de Cramér-von Mises) dos dados, realizou-se a análise de variância (ANOVA). O teste de Tukey foi utilizado para as comparações das médias das variáveis, para as correlações dos dados foi utilizado o teste de correlação de Pearson, e significantes quando p≤ 0,05. Não foram verificadas diferenças significativas (p>0,05) quanto ao número de oócitos recuperados (oócitos totais), oócitos viáveis (G I, II, III), entre os animais tratados (grupos P7 e P14) em relação aos animais que não receberam P4 (grupo P0). As... / Abstract: Progesterone has been used for various purposes in the animal reproduction. The objective of this study was to evaluate the influence of exogenous progesterone injection in the number of recovered oocyte, oocyte quality and embryo production of prepubertal Nelore heifers. We used 31 females (18 to 20 months) non pregnant and without corpus luteum (CL). Cows were divided in 3 groups in a cross-over design: Group I P0 (n=11), animals received two placebo solution applications (1 mL), 7-day interval and starting 14 days (D-14) before the first aspiration (D-0); Group II P7 (n=10) treated group, the animals received a placebo solution application (1 mL) 14 days (D-14) and injecting progesterone (P4; 150 mg) 7 days (D-7) before aspiration; Group III P14 (n = 10), animals received two injections of P4 (150mμg) with an interval of 7 days, the first 14 days (D-14) and the second 7 days (D-7) before aspiration. We conducted 3 aspiration with 28-day intervals. The animals with CL during the experiment were placed in a separate group to be analyzed and compared with the group without CL. The recovered oocytes were selected and submitted to the procedures of the in vitro embryo production (IVEP). After confirming the homocedasticity (BoxCox) and normality (Cramér-von Mises test) of the data, carried out the analysis of variance (ANOVA). Tukey's test was used to compare the means of the variables and the pearson correlation test was used for correlations of the data, considered significant when p ≤ 0.05. There were no significant differences (p> 0.05) in the number of oocytes retrieved (total oocytes), viable oocytes (GI, II, III), between the animals treated (P7 and P14 groups) and animals that did not receive P4 (P0 group). The animals showed an average of 14.98 ± 10.82 oocytes collected by aspiration session. The mean and standard deviation of rates (%) of viable oocytes and embryos produced did not differ (p> 0.05) between groups. The ... / Doutor