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

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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