Vaskivuo T E, Stenbäck F, Karhumaa P, Risteli J, Dunkel L, Tapanainen J S
Department of Obstetrics and Gynecology, University of Oulu, FIN-90220, Oulu, Finland.
Mol Cell Endocrinol. 2000 Jul 25;165(1-2):75-83. doi: 10.1016/s0303-7207(00)00261-6.
Apoptosis has been shown to be an important regulator of endometrium function. To study the regulation of apoptosis in the endometrium during the normal menstrual cycle, the expression of the apoptosis related proteins Bcl-2 and Bax and their correlation to serum estradiol and progesterone, as well as to a replication-related antigen Ki-67 were analyzed. Nine uterine tissue samples and thirty-nine endometrial biopsy specimens were studied. Apoptosis was studied quantitatively by Southern blot analysis of internucleosomal cleavage of genomic DNA, and qualitatively by using in situ 3'-end labeling of fragmented DNA, and Bcl-2, Bax and Ki-67 were detected and quantified immunohistochemically. Apoptotic cells were mostly detected in the glandular epithelium of late secretory and menstruating endometrium. Immunostaining of Ki-67 was detected predominantly in proliferative endometrium. The expression of Bcl-2 was high in proliferative endometrium and decreased in the secretory phase, being very low or absent in the mid- and late secretory and menstruatory phases. Similarly, Bax expression also decreased, but was still present throughout the secretory phase. In human endometrium, apoptosis occurs predominantly in the late secretory and menstrual phases, and is related to alterations in the expression of Bcl-2 and Bax. A decrease in the Bcl-2/Bax ratio in the early secretory phase precedes DNA fragmentation and may predispose the cells to apoptosis.
细胞凋亡已被证明是子宫内膜功能的重要调节因子。为了研究正常月经周期中子宫内膜细胞凋亡的调控机制，分析了凋亡相关蛋白Bcl-2和Bax的表达及其与血清雌二醇、孕酮以及与复制相关抗原Ki-67的相关性。研究了9个子宫组织样本和39个子宫内膜活检标本。通过对基因组DNA核小体间切割进行Southern印迹分析对细胞凋亡进行定量研究，并通过对片段化DNA进行原位3'末端标记进行定性研究，采用免疫组织化学方法检测并定量分析Bcl-2、Bax和Ki-67。凋亡细胞主要在分泌晚期和月经期子宫内膜的腺上皮中检测到。Ki-67免疫染色主要在增殖期子宫内膜中检测到。Bcl-2在增殖期子宫内膜中表达较高，在分泌期降低，在分泌中期和晚期及月经期非常低或不存在。同样，Bax表达也降低，但在整个分泌期仍存在。在人类子宫内膜中，细胞凋亡主要发生在分泌晚期和月经期，并且与Bcl-2和Bax表达的改变有关。分泌早期Bcl-2/Bax比值的降低先于DNA片段化，可能使细胞易于发生凋亡。
