Immunolocalization of bcl-2 protein in human endometrium in the menstrual cycle and simulated early pregnancy

Abstract

Cell death by apoptosis is now regarded as an important feature of normal endometrial physiology. Recent reports have suggested that bcl-2, a proto-oncogene responsible for the suppression of apoptosis, is expressed in endometrium and may be involved in the regulation of menstruation. Using standard immunohistochemical procedures, the immunoreactivity of bcl-2 and progesterone receptors has been investigated in normal human endometrium throughout the menstrual cycle (n = 25) as well as endometrium exposed to continued oestradiol and progesterone stimulation by 'rescue' of corpus luteum (n = 4) with exogenous human chorionic gonadotrophin (HCG) administration (pseudopregnancy). Marked immunoreactivity, consistent with previous reports, was noted in the glandular epithelium during the proliferative phase of the cycle. Immunostaining persisted in the glandular epithelium during the secretory phase, although the percentage and intensity of staining was markedly reduced. Staining in the stromal compartment was only noted during the late secretory phase of the cycle. Co-localization with an antibody against CD56 demonstrated that this immunoactivity largely reflected the presence of lymphocytes in the stroma. Endometrium from subjects who underwent 'luteal rescue' displayed limited immunostaining in either glands or stroma. The absence of significant bcl-2 expression in endocrinologically maintained endometrium makes it highly unlikely that bcl-2 is important in prolonging endometrial cell survival in the luteal phase of the menstrual cycle.