Human Reproduction, Vol. 10, No. 2, pp. 277-286, 1995
© 1995 European Society of Human Reproduction and Embryology
research-article |
Physiology: Site and menstrual cycle-dependent expression of proteins of the tumour necrosis factor (TNF) receptor family, and BCL-2 oncoprotein and phase-specific production of TNF
in human endometrium
Department of Pathology, University of South Florida Health Sciences Center and Moffitt Cancer Center 12902 Magnolia Drive, Tampa, FL 33612, USA 2Department of Obstetrics and Gynecology, Tor Vergata University of Rome Piazzale Umanesimo 10, 00144 Rome, Italy 3Women's Health Institute of California Costa Mesa, CA 92626, USA
Correspondence: 1To whom correspondence should be addressed
Apoptosis in human endometrial epithelium progressively increases from early to late secretory/menstrual phases and remains consistently more prominent in the basalis. It has been suggested that tumour necrosis factor (TNF) 
secreted during the secretory/menstrual phases plays a role in induction of programmed cell death in these cells. In the present study, we characterized expression of receptors of TNF, Fas antigen and BCL-2 in endometrial cells to gain insight as to whether this type of cell death in endometrium may be related to differential or preferential expression of these proteins at specific phases of the menstrual cycle. In addition, to relate production of TNFa to the development of apoptosis, the amount of TNF released by human endometrium was measured. Immunostaining demonstrated that the TNF receptor (TNFr; p55/60)-I, TNFr-II (p75/80) as well as Fas protein were expressed in endometrial epithelium throughout the entire menstrual cycle. This expression was progressively diminished from the basalis towards the upper functionalis. In the proliferative phase, the expression of BCL-2 was prominent in the endometrial glands particularly in those residing in the basalis. This expression became weak as early as the third post-ovulatory day and remained low during the remaining phases of the menstrual cycle. The amount of TNF released by endometrial fragments obtained from various phases of the menstrual cycle was determined. The amount of TNF released into the culture medium by the endometrium was low in the proliferative phase. However, the amount of released TNF progressively increased in the secretory phase and peaked in the menstrual phase. TNFr-I, TNFr-II, Fas, BCL-2 and TNF could be identified by Western blot analysis of proteins extracted from endometrium. Therefore, endometrial epithelium by virtue of expression of receptors of TNF as well as Fas protein is properly poised to respond to ligand signals that regulate apoptosis. Induction of apoptosis in endometrial epithelium and menstrual shedding may be related to loss of the protective effect of BCL-2 as well as to the amount of TNF.
Key words: BCL-2/cytokine/endometrium/tumour necrosis factor
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