{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:14Z","timestamp":1784557214345,"version":"3.55.0"},"reference-count":45,"publisher":"Bioscientifica","issue":"2","license":[{"start":{"date-parts":[[2016,5,1]],"date-time":"2016-05-01T00:00:00Z","timestamp":1462060800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/deed.en_GB"}],"content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:p>\n                    Preparation of mammalian uterus for embryo implantation requires a precise sequence of cell proliferation. In rodent uterus, estradiol stimulates proliferation of epithelial cells. Progesterone operates as a molecular switch and redirects proliferation to the stroma by down-regulating glycogen synthase kinase-3\u03b2 (GSK-3\u03b2) and stimulating \u03b2-catenin accumulation in the periluminal stromal cells. In this study, the WNT signal involved in the progesterone-dependent proliferative switch was investigated. Transcripts of four candidate\n                    <jats:italic>Wnt<\/jats:italic>\n                    genes were measured in the uteri from ovariectomized (OVX) rats, progesterone-pretreated (3 days of progesterone, 2mg\/daily) rats, and progesterone-pretreated rats given a single dose (0.2\u00b5g) of estradiol. The spatial distribution of the WNT proteins was determined in the uteri after the same treatments.\n                    <jats:italic>Wnt5a<\/jats:italic>\n                    increased in response to progesterone and the protein emerged in the periluminal stromal cells of progesterone-pretreated rat uteri. To investigate whether WNT5A was required for proliferation, uterine stromal cell lines were stimulated with progesterone (1\u00b5M) and fibroblast growth factor (FGF, 50ng\/mL). Proliferating stromal cells expressed a two-fold increase in WNT5A protein at 12h post stimulation. Stimulated stromal cells were cultured with actinomycin D (25\u00b5g\/mL) to inhibit new RNA synthesis. Relative\n                    <jats:italic>Wnt5a<\/jats:italic>\n                    expression increased at 4 and 6 h of culture, suggesting that progesterone plus FGF preferentially increased\n                    <jats:italic>Wnt5a<\/jats:italic>\n                    mRNA stability. Knockdown of\n                    <jats:italic>Wnt5a<\/jats:italic>\n                    in uterine stromal cell lines inhibited stromal cell proliferation and decreased\n                    <jats:italic>Wnt5a<\/jats:italic>\n                    mRNA. The results indicate that progesterone initiates and synchronizes uterine stromal cell proliferation by increasing WNT5A expression and signaling.\n                  <\/jats:p>","DOI":"10.1530\/joe-15-0523","type":"journal-article","created":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T23:09:15Z","timestamp":1457996955000},"page":"197-207","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":11,"title":["WINGLESS (WNT) signaling is a progesterone target for rat uterine stromal cell 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