The expressions of vascular endothelial growth factor (VEGF) in rat ovarian follicles and corpus luteum (CL) during different stages of pregnancy and postpartum were investigated. In addition, the effect of tumor necrosis factor-α (TNF-α) on VEGF expression was examined. VEGF mRNA was localized in granulosa cells of preantral follicles, as well as in the granulosa and theca cells of small antral follicles, but not in large antral follicles. VEGF transcripts were amplified in rat CL during pregnancy and postpartum using RT-PCR. The mRNA expression reached the maximal level on day 7, maintained it on days 9-18, decreased after day 18, and was minimal on day 1 postpartum. Western blot showed a 23 ku VEGF protein band in rat CL. Expression of VEGF protein varied in a similar way to that of its mRNA. Treatment with TNF-α at a dosage of 3000 IU/kg on day 4 of pregnancy significantly increased VEGF expression in rat CL. It is suggested that the down-regulation of VEGF expression in large antral follicles may be one factor that contributes to the termination of ovulation in rat ovary during pregnancy. VEGF may be implicated in the CL formation and maintenance via regulating angiogenesis, and its expression is regulated by TNF-α.
In most organs of mammals, cyclic remodelling of tissues after morphogenesis is minimal; however, reproductive tissues of female animals including endometrium, mammary gland, ovarian follicle and corpus luteum undergo growth, maturation and involution at various stages in the reproductive cycle or lifespan of the animal. Reconstruction of the extracellular matrix (ECM) is required for the dynamic tissue reorganization characteristic of these tissues. The ECM consists of proteinaceous and nonproteinaceous molecules that provide the tissue-specific, extracellular architecture to which cells attach. Furthermore, interaction of cellular receptors with proteins of the ECM can regulate cellular structure, second messenger generation and gene expression. Mainte-
The expression and regulation of metallopro-teinases-2, -9 (MMP-2, -9) and their tissue inhibitors TIMP-1, -2, -3 mRNA were studied in this experiment. In the PMSG-hCG primed pseudopregnant rat, MMP-2, -9 mRNA levels were the highest at Day 1, decreased from Day 4, and reached the minimal level at Day 8, then increased at Day 14; no significant changes were observed in TIMP-2 mRNA expression from Day 1 to Day 14; TIMP-3 mRNA expression was the lowest at Day 1, increased from Day 4, reached the maximal level at Day 8, and persisted to Day 14. TNF-α could significantly increase the expression of MMP-2, -9 and TIMP-1 mRNA in the in vitro perfused pseudopregnant CL, and decrease the expression of TIMP-3 mRNA, but had no effect on TIMP-2 mRNA expression. The results indicate that MMP-2, -9 and TIMP-1, -2, -3 might be involved in the regulation of CL function and maintenance of CL structure via their coordinated gene expression. TNF-a could inhibit luteal regression via increasing MMP-2, -9 and TIMP-1 mRNA
