Apoptosis and apoptosis-related proteins in human endometrium

Apoptosis has been shown to be an important regulator of endometrium functi on. To study the regulation of apoptosis in the endometrium during the norm al menstrual cycle, the expression of the apoptosis related proteins Bcl-2 and Bar and their correlation to serum estradiol and progesterone, as well as to a replication-related antigen Ki-67 were analyzed. Nine uterine tissu e samples and thirty-nine endometrial biopsy specimens were studied. Apopto sis was studied quantitatively by Southern blot analysis of internucleosoma l cleavage of genomic DNA, and qualitatively by using in situ 3'-end labeli ng of Fragmented DNA, and Bcl-2. Bar and Ki-67 were detected and quantified immunohistochemically. Apoptotic cells were mostly detected in the glandul ar epithelium of late secretory and menstruating endometrium. Immunostainin g of Ki-67 was detected predominantly in proliferative endometrium. The exp ression 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 a nd menstruatory phases. Similarly, Bar expression also decreased, but was s till present throughout the secretory phase. In human endometrium, apoptosi s occurs predominantly in the late secretory and menstrual phases, and is r elated to alterations in the expression of Bcl-2 and Bar. A decrease in the Bcl-2/Bax ratio in the early secretory phase precedes DNA fragmentation an d may predispose the cells to apoptosis. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.