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The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 1 240-248
Copyright © 1999 by The Endocrine Society

Original Studies

Role of Inflammatory Mediators in Human Endometrium during Progesterone Withdrawal and Early Pregnancy1

H. O. D. Critchley, R. L. Jones, R. G. Lea, T. A. Drudy, R. W. Kelly, A. R. W. Williams and D. T. Baird

Department of Obstetrics and Gynaecology (H.O.D.C., R.L.J., R.G.L., T.A.D., D.T.B.), University of Edinburgh, Medical Research Council Reproductive Biology Unit (R.W.K.), Centre for Reproductive Biology, Edinburgh EH3 9EW; and Department of Pathology (A.R.W.W.), University of Edinburgh, Edinburgh EH8 9AG, United Kingdom

Address all correspondence and requests for reprints to: H. O. D. Critchley, Department of Obstetrics and Gynaecology, University of Edinburgh, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, United Kingdom.

The role of progesterone (P4) in the regulation of inflammatory mediators interleukin-8 (IL-8), monocyte chemoattractant protein-1, and cyclooxygenase-2 (COX-2) and in the recruitment of leukocyte subpopulations in the endometrium has been examined, by employing a model of P4 withdrawal and maintenance in vivo. Messenger RNA and protein expression have been investigated in endometrial biopsies: 1) during the midsecretory phase (LH+8 to 10); during the maintained luteal phase (P4 administered vaginally for 4 days from LH+8) and biopsies collected 2) 24 h and 3) 48 h post withdrawal of P4; and 4) during pseudo pregnancy (lifespan of corpus luteum extended by 7 days with CG; (decidua collected from women with 5) an ectopic gestation and 6) from women undergoing first-trimester termination of pregnancy). CD56+ large granular lymphocytes remain the major leukocyte subtype, both 24 and 48 h after P4 withdrawal, and in decidua (CG supported or ectopic). Higher numbers (P < 0.05) of macrophages (CD68+) were present in endometrium 48 h post P4 withdrawal and in pseudo pregnant endometrium, compared with normal decidua. Significantly more macrophages (P < 0.01) were present in decidua from an ectopic pregnancy. A significant elevation of IL-8 (P < 0.01) and COX-2 (P < 0.05) messenger RNA was detected 48 h post P4 withdrawal. Evidence is provided for up-regulation of IL-8 and COX-2 in response to P4 withdrawal.




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