{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T04:48:35Z","timestamp":1767847715053,"version":"3.49.0"},"reference-count":38,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,11,1]]},"abstract":"<jats:sec><jats:title>Background:<\/jats:title><jats:p>Decidualizing human endometrial stromal cells (HESCs) profoundly up-regulate 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2HSD1), the enzyme that converts inert cortisone to active cortisol. We postulated that the induction of a cortisol gradient upon decidualization of the periimplantation endometrium may impact on the uterine natural killer (uNK) cell population and on local expression of corticosteroid-dependent target genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>Midluteal endometrial biopsies (n = 55) were processed for uNK cell (CD56) analysis and primary HESC cultures. The cultures remained either untreated or were decidualized for 4 or 8 days. A tissue microarray was constructed from endometria with normal (n = 18) and elevated uNK cell (n = 18) scores. An abnormal uNK cell test was defined as greater than 5% CD56+ cells in the subluminal stroma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Increased uNK cell density was associated with lower endometrial expression of 11\u03b2HSD1 and mineralocorticoid receptor (MR) but not glucocorticoid receptor in vivo. Elevated uNK cell density also corresponded to impaired induction of key decidual markers (11\u03b2HSD1, prolactin, and insulin-like growth factor binding protein-1) and MR-dependent enzymes (dehydrogenase\/reductase member 3 and retinol saturase) in differentiating HESC cultures. Increased uNK cell density in vivo was not associated with increased in vitro expression of either IL-15 or IL-11, two cytokines implicated in uNK cell regulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>Elevated levels of uNK cells in the stroma underlying the surface epithelium are associated with inadequate cortisol biosynthesis by resident decidualizing cells and suboptimal induction of key MR-dependent enzymes involved in lipid biogenesis and the retinoid transport pathway. Our observations suggest that uNK cell testing identifies those women at risk of reproductive failure due to relative uterine cortisol deficiency.<\/jats:p><\/jats:sec>","DOI":"10.1210\/jc.2013-1977","type":"journal-article","created":{"date-parts":[[2013,9,12]],"date-time":"2013-09-12T02:52:09Z","timestamp":1378954329000},"page":"4429-4437","source":"Crossref","is-referenced-by-count":46,"title":["Elevated Periimplantation Uterine Natural Killer Cell Density in Human Endometrium Is Associated With Impaired Corticosteroid Signaling in Decidualizing Stromal Cells"],"prefix":"10.1210","volume":"98","author":[{"given":"Keiji","family":"Kuroda","sequence":"first","affiliation":[{"name":"The Division of Reproductive Health (K.K., R.V., S.J., E.S.L., A.S., J.J.B., S.Q.), Clinical Science Research Laboratories, Warwick Medical School, Coventry CV2 2DX, United Kingdom"},{"name":"Department of Obstetrics and Gynaecology (K.K., S.T.), Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radha","family":"Venkatakrishnan","sequence":"additional","affiliation":[{"name":"The Division of Reproductive Health (K.K., R.V., S.J., E.S.L., A.S., J.J.B., S.Q.), Clinical Science Research Laboratories, Warwick Medical School, Coventry CV2 2DX, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean","family":"James","sequence":"additional","affiliation":[{"name":"The Division of Reproductive Health (K.K., R.V., S.J., E.S.L., A.S., J.J.B., S.Q.), Clinical Science Research Laboratories, Warwick Medical School, Coventry CV2 2DX, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"\u0160u\u0107urovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology (S.\u0160., B.M.-J.), Medical School, University of Rijeka, Bra\u0107e Branchetta 20, 51000 Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biserka","family":"Mulac-Jericevic","sequence":"additional","affiliation":[{"name":"Department of Physiology and Immunology (S.\u0160., B.M.-J.), Medical School, University of Rijeka, Bra\u0107e Branchetta 20, 51000 Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma S.","family":"Lucas","sequence":"additional","affiliation":[{"name":"The Division of Reproductive Health (K.K., R.V., S.J., E.S.L., A.S., J.J.B., S.Q.), Clinical Science Research Laboratories, Warwick Medical School, Coventry CV2 2DX, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology (K.K., S.T.), Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anatoly","family":"Shmygol","sequence":"additional","affiliation":[{"name":"The Division of Reproductive Health (K.K., R.V., S.J., E.S.L., A.S., J.J.B., S.Q.), Clinical Science Research Laboratories, Warwick Medical School, Coventry CV2 2DX, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan J.","family":"Brosens","sequence":"additional","affiliation":[{"name":"The Division of Reproductive Health (K.K., R.V., S.J., E.S.L., A.S., J.J.B., S.Q.), Clinical Science Research Laboratories, Warwick Medical School, Coventry CV2 2DX, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siobhan","family":"Quenby","sequence":"additional","affiliation":[{"name":"The Division of Reproductive Health (K.K., R.V., S.J., E.S.L., A.S., J.J.B., S.Q.), Clinical Science Research Laboratories, Warwick Medical School, Coventry CV2 2DX, United 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