Cyclic changes of vasculature and vascular phenotypes in normal human ovaries

In order to study alterations of angiogenesis and blood vessel regression through ovarian cycle in human ovaries we quantitatively examined vascularity in various stages in 24 normal human ovaries. Vascular density (VD; vessel numbers/10^-7 m²) and endothelial area of each vessel (EA; 10^-12 m²/vessel) were evaluated using immunohistochemistry of CD34 and CAS 200 image analysis system. Small-sized vessels were sporadically observed in stroma adjacent to primordial or primary follicles (6.73 ± 1.83 for VD and 113.58 ± 21.80 for EA). Formation of capillary network was observed in the theca layer of preantral follicles (PA; 15.28 ± 2.77 for VD and 113.58 ± 21.80 for EA), and higher density of the capillary network was detected in non-dominant follicles in follicular phase (ND-F) and dominant follicles (DF; 29.33 ± 3.84 for VD and 179.69 ± 41.25 for EA). Dense capillary network was still present in non-dominant follicles in luteal phase (ND-L) and atretic follicles (AF; 26.88 ± 3.36 for VD and 110.88 ± 50.53 for EA). After ovulation, developing capillaries were also observed in the luteinized granulosa layers in early corpus luteum (21.95 ± 2.06 for VD and 167.08 ± 29.59 for EA). Vessel density markedly increased in mid corpus luteum, reached plateau in late corpus luteum (60.85 ± 5.92 for VD and 70.99 ± 15.57 for EA) and remained constant during degenerating corpora lutea. Vascular endothelial growth factor was immunohistochemically observed in the theca cells in PA, ND-F, DF and ND-L in follicular stages, and functioning corpora lutea. Immunoreactivity of intercellular adhesion molecule-1 was detected only in post-capillary venules in early degenerating corpora lutea. These findings suggest that ovarian angiogenesis is a requirement for the early stages of folliculogenesis and luteal growth, and also plays an important role in the process of follicular atresia and luteal regression.