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Molecular characterization of PRM-associated endometrial changes, PAEC, following mifepristone treatment
Department of Women´s and Children´s Health, Division of Obstetrics and Gynecology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Department of Women´s and Children´s Health, Division of Obstetrics and Gynecology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Department of Women´s and Children´s Health, Division of Obstetrics and Gynecology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Department of Women´s and Children´s Health, Division of Obstetrics and Gynecology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
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2018 (English)In: Contraception, ISSN 0010-7824, E-ISSN 1879-0518, Vol. 98, no 4, p. 317-322Article in journal (Refereed) Published
Abstract [en]

Objective: The progesterone receptor modulator (PRM) mifepristone holds the potential to be developed for regular contraception. However, long-term treatment can cause thickening of the endometrium and PRM-associated endometrial changes (PAEC). The objective of this study was to explore the molecular expression of endometrium displaying PAEC after mifepristone treatment in order to understand the future implications of PAEC and safety of long-term use. Study design: Endometrial biopsies were obtained from premenopausal women following 3 months of continuous mifepristone treatment. The biopsies were evaluated regarding occurrence of PAEC and followed up by a comparative analysis of gene expression in PAEC endometrium (n=7) with endometrium not displaying PAEC (n=4). Methods used included microarray analysis, Ingenuity Pathway Analysis (IPA) and real-time polymerase chain reaction. Results: Three genes relevant within endometrial function were up-regulated with PAEC: THY1 (p=.02), ADAM12 (p=.04) and TN-C (p=.04). The proliferation marker MKi67 was not altered (p=.31). None of the differentially regulated genes were involved in the endometrial cancer-signaling pathway (based on IPA knowledge database). Conclusion: The genes altered in endometrium displaying PAEC after 3 months of mifepristone exposure are mainly involved in the structural architecture of tissue. Implications: PAEC features may be explained by the altered genes and their networks affecting tissue architecture although not involved in endometrial cancer signaling pathways, and thus, treatment with mifepristone at this dosage does not show any adverse effect at endometrial level.

Place, publisher, year, edition, pages
Elsevier, 2018. Vol. 98, no 4, p. 317-322
Keywords [en]
Endometrium, Mifepristone, PAEC, Progesterone receptor modulator
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Analytical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-360879DOI: 10.1016/j.contraception.2018.05.020ISI: 000445973800013PubMedID: 29890128OAI: oai:DiVA.org:uu-360879DiVA, id: diva2:1249606
Funder
Swedish Research Council, 2012-01981Stockholm County CouncilAvailable from: 2018-09-19 Created: 2018-09-19 Last updated: 2018-12-03Bibliographically approved

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Hörnaeus, KatarinaFalk, AlexanderRamström, Margareta
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