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Here, we aimed to investigate the effect of mifepristone, a selective progesterone receptor modulator of ovarian mesenchymal stem\/stromal cells (MSC<\/jats:styled-content>) from BRCA<\/jats:styled-content><\/jats:italic>1\u2212\/2\u2212<\/jats:italic><\/jats:sup> carriers.<\/jats:p><\/jats:sec>Material and methods<\/jats:title>Ovarian BRCA<\/jats:styled-content><\/jats:italic>1\u2212\/2\u2212<\/jats:italic><\/jats:sup> MSC<\/jats:styled-content> were positively selected using the markers CD<\/jats:styled-content>90, CD<\/jats:styled-content>73 and CD<\/jats:styled-content>105 from nine healthy women. The effect of dose response and combination treatment with mifepristone and analogs of progesterone\u2010 or glucocorticoid\u2010receptors were investigated on BRCA<\/jats:styled-content><\/jats:italic>1\u2212\/2\u2212<\/jats:italic><\/jats:sup> MSC<\/jats:styled-content> in vitro using a panel of markers for proliferation (ki67, BrdU, CDK<\/jats:styled-content>2, p21<\/jats:italic>CIP<\/jats:italic><\/jats:sup><\/jats:styled-content>), apoptosis (BAX<\/jats:styled-content>, BCL<\/jats:styled-content>2, CASPASE<\/jats:styled-content>3<\/jats:italic>), tumor suppression (TP<\/jats:styled-content>53, PTEN<\/jats:styled-content><\/jats:italic>) and cell survival (PI<\/jats:styled-content>3KCA<\/jats:styled-content>, MAPK<\/jats:styled-content>3,<\/jats:italic> mTOR<\/jats:italic><\/jats:styled-content>).<\/jats:p><\/jats:sec>Results<\/jats:title>The dose response with mifepristone treatment suggested an optimal effect with 10\u00a0\u03bcm<\/jats:sc> mifepristone, exhibiting >90% viability and significantly reducing growth signaling markers (TP<\/jats:styled-content>53<\/jats:italic> and MAPK<\/jats:styled-content>3)<\/jats:italic>. Furthermore, combined treatment with progesterone plus mifepristone (PG+MIFE) gave an enhanced anti\u2010proliferative effect in comparison with hydrocortisone plus mifepristone (HC+MIFE) by significantly reducing markers of proliferation (BrdU+<\/jats:sup> and Ki67<\/jats:italic> expression) and tumor suppressors (PTEN<\/jats:styled-content>, TP<\/jats:styled-content>53<\/jats:italic>), and increasing the percentage of pro\u2010apoptotic cells. Consequently, accumulation of p21<\/jats:italic>CIP<\/jats:italic><\/jats:sup><\/jats:styled-content> together with reduced levels of CDK<\/jats:styled-content>2 confirms growth inhibition by reversibly arresting cell\u2010cycle progression at the G1\u2010S phase, not by inducing apoptosis.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Our study showed an anti\u2010proliferative effect on ovarian BRCA<\/jats:styled-content><\/jats:italic>1\u2212\/2\u2212<\/jats:italic><\/jats:sup> MSC<\/jats:styled-content> on in vitro combined treatment with mifepristone and progesterone. These findings suggest that mifepristone or other selective progesterone receptor modulators could be developed as a preventive treatment and postpone early use of prophylactic salpingo\u2010oophorectomy as well as reduce the risk of ovarian cancer.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aogs.13485","type":"journal-article","created":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T14:17:38Z","timestamp":1539699458000},"page":"250-261","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Mifepristone mediates anti\u2010proliferative effect on ovarian mesenchymal stem\/stromal cells from female BRCA<\/scp><\/i>1\u2212\/2\u2212<\/i><\/sup> carriers"],"prefix":"10.1111","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6820-1341","authenticated-orcid":false,"given":"Sakthivignesh","family":"Ponandai\u2010Srinivasan","sequence":"first","affiliation":[{"name":"Division of Obstetrics and Gynecology Department of Women's and Children's Health Karolinska Institutet and Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parameswaran G.","family":"Lalitkumar","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Gynecology Department of Women's and Children's Health Karolinska Institutet and Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Garcia","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Gynecology Department of Women's and Children's Health Karolinska Institutet and Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suby Jo","family":"Varghese","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Gynecology Department of Women's and Children's Health Karolinska Institutet and Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3006-4107","authenticated-orcid":false,"given":"Joseph W.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Division of Pathology and Cytology Department of Oncology and Pathology Karolinska Institutet and Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6516-1444","authenticated-orcid":false,"given":"Kristina","family":"Gemzell\u2010Danielsson","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Gynecology Department of Women's and Children's Health Karolinska Institutet and Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1068-9732","authenticated-orcid":false,"given":"Angelique","family":"Floter 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