Abstract

we have studied the implication of bone morphogenetic proteins (BMP) in the ovarian physiology. In the present study,weexhibit ourdata regarding (1) folliculogenesis, (2) ovulation and (3) polycystic ovary syndrome (PCOS), especially from the point of the relationship between ovarian cells and immune-competent cells. Folliculogenesis:Although the formation of an individual capillary network in the theca cell layer is required for ovarian folliculogenesis, the mechanism has not been clarified. We found that theca cell derived BMP-7 stimulated VEGF secretion levels in GC significantly. In endothelial cells, BMP-7 increased the cell number and induced VEGF receptor mRNA. BMP-7 might work to form vasculature around follicles via induction of VEGF expression in GC and increased sensitivity of endothelial cells to VEGF. Ovulation: As granulocyte colony-stimulating factor (G-CSF) is known to be a candidate for a treatment of luteinized unruptured follicle (LUF), neutrophils might be involved in ovulatory process. BMP cytokine is known to regulate ovulation, as BMP-6 null mice exhibit a decrease in the number of ovulatory follicleswithout effect on either themorphology or the dynamics of follicular development. We found that BMP-6 significantly increased growthregulated oncogene (GRO)levels in human GC. On the other hand, BMP-6 suppressed the relative expression of the protease inhibitors, secretory leukocyte peptidase inhibitor (SLPI) in GC. BMP-6 might play a role in ovulation by increasing the accumulation of neutrophils in the ovulatory follicle and suppressing the effect of protease inhibitor. PCOS: Plasminogen activator inhibitor-1 (PAI-1), the main physiological inhibitor of plasminogen activation, is elevated in women with PCOS and has been linked to PCOS in a mouse model of the disease. We have found that TGFand TNFwhich are involved in the etiology of PCOS, increased PAI-1 secretion levels by cultured GC. Insulin sensitizing drugs suppressed TGFand TNFmRNA expression in peritoneal fluid mononuclear cells. Our data suggested that insulin sensitizing agentsmayprovide a potential therapy for PCOS via down regulation of PAI-1 expression indirectly. To understand the etiology of PCOS, the regulation of immune-competent cells should be taken into consideration.

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