Role of inflammatory mediators in human endometrium during progesterone withdrawal and early pregnancy

• Published in: The journal of clinical endocrinology and metabolism 1999, Vol.84 (1), p.240-248
• Main Authors: CRITCHLEY, H. O. D, JONES, R. L, LEA, R. G, DRUDY, T. A, KELLY, R. W, WILLIAMS, A. R. W, BAIRD, D. T
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chemokine CCL2 - physiology; Cyclooxygenase 2; Dinoprost - physiology; Endometrium - physiology; Enzyme-Linked Immunosorbent Assay; Estradiol - blood; Female; Fundamental and applied biological sciences. Psychology; Hormone metabolism and regulation; Humans; Immunohistochemistry; Inflammation Mediators - physiology; Interleukin-8 - physiology; Isoenzymes - physiology; Leukocytes - physiology; Mammalian female genital system; Membrane Proteins; Pregnancy - physiology; Progesterone - blood; Progesterone - physiology; Prostaglandin-Endoperoxide Synthases - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Vertebrates: reproduction
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.84.1.240

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.