Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Hum Reprod. 2010 Mar;25(3):642-53. doi: 10.1093/humrep/dep437. Epub 2009 Dec 15.
Information is limited regarding the multifunctional role of GnRH agonist (GnRHa) therapy in reproductive diseases. We investigated the pattern of changes in inflammatory reaction, micro-vessel density and apoptosis in the tissues collected from women with endometriosis, adenomyosis and uterine myoma who were treated with or without GnRHa therapy.
Biopsy specimens were collected from lesions, myometria and corresponding endometria of 45 women with ovarian endometrioma, 35 women with adenomyosis and 56 women with uterine myoma. A fraction of these women were treated with GnRHa therapy for a variable period of 3-6 months before surgery. We performed immunohistochemical analysis of CD68, a macrophage (Mvarphi) marker and von Willebrand factor (VWF), a vessel marker, using respective antibodies. Changes in apoptosis were examined using TdT-mediated dUTP-biotin nick end-labeling assay and by the immunoexpression of activated caspase-3 in tissues after GnRHa therapy.
The infiltration of CD68-positive Mvarphi and VWF-positive micro-vessel density were significantly decreased in the endometria of women with endometriosis, adenomyosis and uterine myoma in the GnRHa-treated group when compared with that in the non-treated group. Marked decreases in inflammatory and angiogenic responses were observed in lesions and myometria of these diseases. When compared with the non-treated group, a significant increase in apoptotic index (apoptotic cells per 10 mm(2) area) and quantitative-histogram scores of activated caspase-3 after GnRHa therapy were observed in the eutopic endometria, lesions and myometria of these diseases.
GnRHa was able to markedly reduce the inflammatory reaction and angiogenesis and to significantly induce apoptosis in tissues derived from women with endometriosis, adenomyosis and uterine myoma. These multiple biological effects at the tissue level may be involved in the regression of these reproductive diseases.
关于 GnRH 激动剂（GnRHa）治疗在生殖系统疾病中的多功能作用的信息有限。我们研究了接受或未接受 GnRHa 治疗的子宫内膜异位症、子宫腺肌病和子宫肌瘤患者的组织中炎症反应、微血管密度和细胞凋亡的变化模式。
从 45 名卵巢子宫内膜异位症患者、35 名子宫腺肌病患者和 56 名子宫肌瘤患者的病变、子宫肌层和相应的子宫内膜中采集活检标本。其中一部分患者在手术前接受了 3-6 个月的 GnRHa 治疗。我们使用各自的抗体对 CD68（巨噬细胞标志物）和血管标志物 von Willebrand 因子（VWF）进行了免疫组织化学分析。在 GnRHa 治疗后，通过 TdT 介导的 dUTP-生物素缺口末端标记法（TUNEL）和组织中活化的 caspase-3 的免疫表达检测细胞凋亡的变化。
与未治疗组相比，接受 GnRHa 治疗的子宫内膜异位症、子宫腺肌病和子宫肌瘤患者的子宫内膜中 CD68 阳性巨噬细胞和 VWF 阳性微血管密度的浸润显著减少。这些疾病的病变和子宫肌层中的炎症和血管生成反应明显减少。与未治疗组相比，接受 GnRHa 治疗后，这些疾病的在位子宫内膜、病变和子宫肌层中的细胞凋亡指数（每 10mm² 面积的凋亡细胞数）和活化 caspase-3 的定量直方图评分显著增加。
GnRHa 能够显著减少组织中的炎症反应和血管生成，并显著诱导子宫内膜异位症、子宫腺肌病和子宫肌瘤患者的组织发生细胞凋亡。这些组织水平的多种生物学效应可能与这些生殖系统疾病的消退有关。
