Expression of matrix metalloproteinases to induce the expression of genes associated with apoptosis during corpus luteum development in bovine

Here we investigated the expressions of apoptosis-associated genes known to induce programmed cell death through mRNA expressions of two matrix metalloproteinases (MMPs) that are involved in the degradation of collagen and basal membrane in luteal cells cultured in the treatment media. Our results show that the activity of MMP-2 gelatinase was higher in the CL2 and CL1 of luteal phase, was gradually decreased in the CH2 and CH3 of luteal phase. In particular, the expressions of P4-r and survival-associated genes (IGFr, PI3K, AKT, and mTOR) were strongly induced during CL3 stage, whereas the levels of these genes in CL were lower during CL2 and CL1 stages. And in the cultured lutein cell analyzed result, we found that as MMPs increase, genes related to apoptosis ( 20α-HSD and Casp-3) also increase. In other words, the results for P4-r and survival-related gene expression patterns in the luteal cells were contrary to the MMPs activation results. These results indicate that active MMPs are differentially expressed to induce the expression of genes associated with programmed cell death from the degrading luteal cells. Therefore, our results suggest that the MMPs activation may lead to luteal cell development or death.

Expression of matrix metalloproteinases to induce the expression of genes associated with apoptosis during corpus luteum development in bovine

Here we investigated the expressions of apoptosis-associated genes known to induce programmed cell death through mRNA expressions of two matrix metalloproteinases (MMPs) that are involved in the degradation of collagen and basal membrane in luteal cells cultured in the treatment media. Our results show that the activity of MMP-2 gelatinase was higher in the CL2 and CL1 of luteal phase, was gradually decreased in the CH2 and CH3 of luteal phase. In particular, the expressions of P4-r and survival-associated genes (IGFr, PI3K, AKT, and mTOR) were strongly induced during CL3 stage, whereas the levels of these genes in CL were lower during CL2 and CL1 stages. And in the cultured lutein cell analyzed result, we found that as MMPs increase, genes related to apoptosis ( 20α-HSD and Casp-3) also increase. In other words, the results for P4-r and survival-related gene expression patterns in the luteal cells were contrary to the MMPs activation results. These results indicate that active MMPs are differentially expressed to induce the expression of genes associated with programmed cell death from the degrading luteal cells. Therefore, our results suggest that the MMPs activation may lead to luteal cell development or death.

Differential Release of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases by Human Granulosa-Lutein Cells and Ovarian Leukocytes

Tissue reorganization during ovulation and corpus luteum formation involves a coordinated action of matrix metalloproteinases (MMPs) and tissue MMP inhibitors (TIMPs). In this study we investigated the cellular source of ovarian MMPs and TIMPs. Cells isolated from the preovulatory human follicle were cultured after immunobead depletion of CD45-expressing cells, which allowed differential assessment of leukocyte and granulosa-lutein cell fractions. Secretion of MMP-9 by follicular fluid-derived cells was associated with the presence of leukocytes. Granulosa-lutein cells synthesized low levels of MMP-9 but failed to secrete this enzyme that presumably accumulated in the cytoplasm, indicated by an increased MMP-9 expression of luteinized cells in sectioned midluteal phase corpora lutea. Synthesis and secretion of TIMP by follicular fluid-derived cells was associated with granulosa-lutein cells. TIMPs derived by granulosa-lutein cells failed to inhibit MMP-related pericellular proteolysis. The findings support a two-cell model of periovulatory MMP/TIMP release, in which leukocytes secrete MMPs and granulosa-lutein cells release TIMP, suggesting that there exists an intriguing interaction among cells that intertwingle during ovulation and corpus luteum formation.