Er follicle lumen; the surrounding thin layer of thecal cells are weakly VEGF-positive, and EG-VEGF-negative; EG-VEGF (F) is expressed within the thecal cells with the upper follicle in which the granulosa cell layer has degenerated. Granulosa cells (GC), theca (Th), stroma (St), lumen (L). Scale bars: 200 m (A, D, G, J, M); one hundred m (B, C, E, F, H, I, K, L, N, O).VEGF and EG-VEGF in Human Ovaries 1891 AJP June 2003, Vol. 162, No.Figure 9. Correlation involving expression of VEGF or EG-VEGF and vascularity, as assessed by expression of CD34, in representative PCOS specimens. Parallel sections have been immunostained with anti-CD34 (QBEnd/10, E) or hybridized with EG-VEGF anti-sense (I), VEGF anti-sense (M), EG-VEGF sense (Q), and VEGF sense (U) riboprobes. H E images (A) are shown for reference. In PCOS ovaries, EG-VEGF expression is higher within the theca surrounding atretic follicle lumens (A, B, I, J) and diffusely in ovarian stroma (C, D, K, L), whereas VEGF expression in these areas (Q) is weak or absent. Vascularity in corresponding areas is illustrated by CD34 immunostaining (E). Related, even though weaker immunostaining was observed with anti-CD31 monoclonal antibody JC/70A (not shown). Scale bars, 100 m.opment of a capillary plexus, but becomes pretty much undetectable by mid-luteal phase. In contrast, EG-VEGF starts being expressed later than VEGF but persists no less than by way of mid-luteal phase, when it can be strongly expressed by theca lutein cells surrounding blood vessels. As a result, EG-VEGF may perhaps be specifically critical for the formation of a extra mature vascular bed that contains arterioles and as a result for the persistence and adequacy of luteal function. In our initial report we didn’t detect Complement Factor B Proteins site considerable expression of EG-VEGF in the CL.18 The restricted series examined plus the stage-specific expression of EG-VEGF mRNA inside the CL are likely explanations for such lack of detection. Particularly higher expression of EG-VEGF (but not VEGF) mRNA was demonstrated in hilus cells.30 Thesecells are believed to be the functional equivalent of Leydig cells within the ovary, as hyperplastic or neoplastic modifications affecting them are identified to lead to a masculinizing syndrome.30 2 The intimate partnership of hilus cells with blood vessels and nerve terminals was noted even within the earliest research.31,32 Intriguingly, Bv8, a protein obtaining a higher degree of homology with EG-VEGF and in a position to Checkpoint Kinase 2 (Chk2) Proteins Source interact with all the similar binding web sites,33 has been shown to possess neurotrophic35 and neuromodulator36 functions. Despite the fact that Bv8 mRNA is undetectable within the human ovary, it is tempting to speculate that EG-VEGF might play both an angiotrophic and neurotrophic role in this context. However, these findings are correlative in nature and inhibition research with monoclonal antibodies or other inhibitors, performed at different stages within the cycle, will1892 Ferrara et al AJP June 2003, Vol. 162, No.be expected to dissect the physiological roles of EG-VEGF inside the ovary. It is well established that elevated ovarian mass, supported by new blood vessel proliferation in stroma and theca, is a crucial function of PCOS. Certainly, there has been considerable interest within the identification of the mediators of such hypervascularity, but surprisingly little is recognized about the nature and distribution of such mediators. The present study may represent essentially the most substantial series reported so far examining the in situ expression of candidate angiogenic factor genes in PCOS. Recent literature has focused on VEGF as one of the most lik.
