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Endometrial Inhibin/Activin β-B Subunit Expression Is Related to Decidualization and Is Reduced in Tubal Ectopic Pregnancy

Divisions of Reproductive and Developmental Sciences (A.W.H., S.v.d.D., A.E.K., M.M., P.L., H.O.D.C., W.C.D.), Pathway Medicine (S.B., P.G.), and Pathology (A.R.W.), The University of Edinburgh, Edinburgh EH16 4SB, United Kingdom; and Centre for Protein and Peptides (H.L.), Oxford Brookes University, Oxford OX3 0BP, United Kingdom

Address all correspondence and requests for reprints to: Dr. Andrew W. Horne, Obstetrics and Gynaecology, University of Edinburgh, Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SB, United Kingdom. E-mail: andrew.horne{at}ed.ac.uk.

Context: Ectopic pregnancy is common but remains difficult to diagnose accurately. There is no serum test to differentiate ectopic from intrauterine gestation.

Objective: Our objective was to investigate differential gene expression in decidualized endometrium of ectopic pregnancy.

Design: Tissue and serum analysis informed by microarray study was performed.

Setting: The study was performed at a large United Kingdom teaching hospital.

Patients or Other Participants: Women undergoing surgical termination of pregnancy (n = 8), evacuation of uterus for miscarriage (n = 6), and surgery for tubal ectopic pregnancy (n = 11) were included in the study. Endometrium was collected from normally cycling women undergoing hysterectomy.

Interventions: Decidualized endometrium was subjected to microarray analysis, morphological assessment, and immunohistochemistry. Endometrial stromal fibroblasts were cultured in the presence of decidualizing stimuli.

Main Outcome Measures: Differential expression of potentially secreted molecules was calculated.

Results: Inhibin/activin β-B expression was lower in decidualized endometrium from ectopic pregnancies when compared with that of ongoing pregnancies (P < 0.01) or miscarriages (P < 0.01). The localization of the β-B subunit was more marked in decidualized than nondecidualized stroma. Decidualization of stromal fibroblasts in vitro was associated with increased β-B expression (P < 0.05). Endometrial stroma of ectopic pregnancies was less decidualized morphologically (P < 0.05), with lower prolactin (P < 0.01) and IGF binding protein-1 (P < 0.005) expression. Serum activin B was lower in ectopic pregnancies (P < 0.005) than in intrauterine pregnancies, whereas there was no difference in progesterone concentrations.

Conclusions: Despite similar concentrations of progesterone, the endometrium of ectopic pregnancies is less decidualized than intrauterine pregnancies. Expression of the β-B subunit is related to decidualization and can be detected in the circulation as activin B. Serum activin B concentrations are lower in ectopic pregnancy.

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