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.
The clinical and pathological features of an apparently unique case of an endometrial cyst of the uterus are reported. The cyst was located within the myometrium of a 16-year-old woman suffering from dysmenorrhea. After excision of the cyst, patient's symptoms improved. On histological examination, the cyst most closely resembled an adenomyotic cyst.
We evaluated the immunolocalization of the steroidogenic enzymes involved in the production of ovarian steroids, including the cholesterol side-chain cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase (HSD), 17alpha-hydroxylase (P450c17) and aromatase (P450arom), oestrogen receptor (ER) and androgen receptor (AR), a steroidogenic transcription factor. Ad4-binding protein (Ad4BP) and a cell cycle-related nuclear antigen, Ki67, in five patients with polycystic ovarian syndrome (PCOS). Results were compared with those from normal cycling human ovaries to study in situ ovarian steroidogenesis and cell proliferation in polycystic ovaries (PCO). We classifed the follicles morphologically according to the development of granulosa types: type A, more than four layers (n = 7); type B, one to three layers (n = 11); and type C, theca interna cells only (n = 21). ER and P450arom were not observed in any of the follicles examined. In type A follicles, P450scc, 3beta-HSD, P450c17, AR and Ad4BP were observed in theca cells in all seven follicles examined, but the granulosa cells were positive only for Ad4BP (4/7) and AR (7/7). These immunohistolocalization patterns resembled those in non-selected antral follicles of normally cycling human ovaries. In theca cells from types B and C follicles, follicles positive for the steroidogenic enzymes, AR and Ad4BP were decreased in number. There were no significant differences between types A and B PCO follicles in the Ki67 labelling index of granulosa or theca cells, and between PCO and antral follicles from normally cycling human ovaries. Data demonstrate that the follicles of PCO are by no means atretic and are actively involved in both steroidogenesis and cell proliferation. The absence of ER and aromatase expression in the granulosa cells of PCO may be important in abnormal follicular development in patients with PCOS.
We investigated, using an image analysis system, the immunohistochemical localization of leukocyte subpopulations and human leukocyte antigen (HLA)-DR in 30 normal-cycling human ovaries in order to better understand local immunological events in human ovaries. All subtypes of T lymphocytes examined (CD3+, CD4+ and CD8+ cells) were sporadically observed in the stroma and theca layers of follicles throughout the menstrual cycle (ranging from 4.32 to 6.25 cells/10(-7) m2, 1.67 to 3.33 cells/10(-7) m2 and 2.33 to 3.44 cells/10(-7) m2, respectively for the three subtypes), and subsequently, increased in number in atretic follicles (78.70 +/- 6.90, 31.13 +/- 2.54 and 43.31 +/- 3.35). After ovulation, the number of T lymphocytes was markedly low in the early and mid corpus luteum (13.88 +/- 1.62, 4.18 +/- 0.50 and 6.53 +/- 0.45). The number increased in the late corpus luteum, and was highest in the late degenerating corpus luteum (255.67 +/- 27.10, 102.12 +/- 7.80 and 137.34 +/- 12.50). HLA-DR was sporadically positive in fibroblasts in the stroma and theca layers of follicles (means ranged from 1.25 to 1.82 cells/10(-7) m2), and increased in atretic follicles (24.68 +/- 2.25). HLA-DR+ cells were markedly low in the early and mid corpus luteum (2.16 +/- 0.88), increased in the late corpus luteum, and reached a plateau in the late degenerating corpus luteum (121.84 +/- 17.73). The great majority of these increased HLA-DR+ cells were macrophages. Results of our study suggest that T lymphocytes and/or macrophages play important roles in luteal regression and follicular atresia in normal-cycling human ovaries.
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