Leukocyte Populations and Steroid Receptor Expression in Human First-Trimester Decidua; Regulation by Antiprogestin and Prostaglandin E Analog

• Published in: The journal of clinical endocrinology and metabolism Vol. 90; no. 7; pp. 4315 - 4321
• Main Authors: Milne, Stuart A, Henderson, Teresa A, Kelly, Rodney W, Saunders, Philippa T, Baird, David T, Critchley, Hilary O. D
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.07.2005
• Subjects: Abortifacient Agents - pharmacology; Alprostadil - analogs & derivatives; Alprostadil - pharmacology; Biological and medical sciences; Decidua - chemistry; Decidua - cytology; Decidua - drug effects; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Hormone Antagonists - pharmacology; Humans; Immunohistochemistry; Killer Cells, Natural - drug effects; Leukocyte Count; Macrophages - drug effects; Medical sciences; Mifepristone - pharmacology; Neutrophils - drug effects; Pregnancy; Pregnancy Trimester, First; Receptors, Androgen - analysis; Receptors, Estrogen - analysis; Receptors, Progesterone - analysis; Vertebrates: endocrinology; Human; Leukocyte; First trimester; Steroid hormone receptor; Decidua; Pregnancy; Regulation(control); Uterus; Analog; Female genital system; Antiprogesterone; Prostaglandin E; Endocrinology; Hormonal receptor
• DOI: 10.1210/jc.2004-2338
• ISSN: 0021-972X

Context: Progesterone acting via its cognate receptor is critical to maintaining a viable endometrial environment for implantation and pregnancy. During medical termination of pregnancy, the biological effect of progesterone is pharmacologically withdrawn and prostaglandins administered exogenously. Leukocytes within the uterus are the effector cells of an inflammatory response and play important roles in both tissue breakdown and remodeling. Objective: The aim of this study was to identify the separate and combined effects of the antiprogestin Mifepristone (single dose, 200 mg) and the prostaglandin E (PGE) analog (gemeprost) on leukocyte populations and steroid receptor expression in human first-trimester decidua. Patients: Eighty women were recruited from the termination of pregnancy service with a gestational age of between 35 and 65 d at the time of surgical termination of pregnancy. Main Outcome Measures: Immunohistochemistry was used to measure macrophage (CD68 +ve), neutrophil (neutrophil elastase +ve), and uterine natural killer cell (CD56 +ve) populations and progesterone (PRA and PRB), estrogen (ERα and ERβ), and androgen receptor (AR) expression. Results: After administration of both antiprogestin and the PGE analog, macrophage and neutrophil numbers were significantly increased, whereas natural killer cell numbers were unchanged. Antiprogestin and PGE analog coadministration also significantly decreased PR and ERα immunoreactivity but had no effect on androgen receptor or ERβ receptor expression. PGE analog alone was also capable of reducing PR expression. Conclusions: In this study, we demonstrate that the inflammatory response induced by antiprogestin in combination with PGE analog is accompanied by both increases in macrophages and neutrophils numbers and decreases in PR and ERα expression in human first-trimester decidua.