{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:23:11Z","timestamp":1789204991993,"version":"build-2803163510"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"35","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,8,31]]},"abstract":"<jats:p>\n                    Immunophilin FK506-binding protein 52 (FKBP52) is a cochaperone that binds to the progesterone receptor (PR) to optimize progesterone (P\n                    <jats:sub>4<\/jats:sub>\n                    )-PR signaling. We recently showed that\n                    <jats:italic>Fkbp52<\/jats:italic>\n                    -deficient (\n                    <jats:italic>Fkbp52<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice have reduced uterine PR responsiveness and implantation failure which is rescued by excess P\n                    <jats:sub>4<\/jats:sub>\n                    supplementation in a genetic background-dependent manner. This finding led us to hypothesize that FKBP52 has functions in addition to optimizing PR activity. Using proteomics analysis, we found that uterine levels of peroxiredoxin-6 (PRDX6), a unique antioxidant, are significantly lower in\n                    <jats:italic>Fkbp52<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice than in WT and PR-null (\n                    <jats:italic>Pgr<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice. We also found that\n                    <jats:italic>Fkbp52<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice with reduced uterine PRDX6 levels are susceptible to paraquat-induced oxidative stress (OS), leading to implantation failure even with P\n                    <jats:sub>4<\/jats:sub>\n                    supplementation. The same dose of paraquat did not interfere with implantation in WT mice. Moreover, treatment with antioxidants \u03b1-tocopherol and N-acetylcysteine (NAC) attenuated paraquat-induced implantation failure in P\n                    <jats:sub>4<\/jats:sub>\n                    -treated\n                    <jats:italic>Fkbp52<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Functional analyses using mouse embryonic fibroblasts show that\n                    <jats:italic>Fkbp52<\/jats:italic>\n                    deficiency associated with reduced PRDX6 levels promotes H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -induced cell death, which is reversed by the addition of NAC or by forced expression of PRDX6, suggesting that\n                    <jats:italic>Fkbp52<\/jats:italic>\n                    deficiency diminishes the threshold against OS by reducing PRDX6 levels. These findings provide evidence that heightened uterine OS in\n                    <jats:italic>Fkbp52<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    females with reduced PRDX6 levels induces implantation failure even in the presence of excess P\n                    <jats:sub>4<\/jats:sub>\n                    . This study shows that FKBP52\u2013PRDX6 signaling protects pregnancy from overt OS.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1009324107","type":"journal-article","created":{"date-parts":[[2010,8,17]],"date-time":"2010-08-17T00:40:39Z","timestamp":1282005639000},"page":"15577-15582","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":60,"title":["Uterine FK506-binding protein 52 (FKBP52)\u2013peroxiredoxin-6 (PRDX6) signaling protects pregnancy from overt oxidative stress"],"prefix":"10.1073","volume":"107","author":[{"given":"Yasushi","family":"Hirota","sequence":"first","affiliation":[{"name":"Division of Reproductive Sciences, The Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229;"},{"name":"Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuray","family":"Acar","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences, The Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229;"},{"name":"Department of Histology and Embryology, School of Medicine, Akdeniz University, Antalya 07070, Turkey; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Tranguch","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences, The Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin E.","family":"Burnum","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Research Center, Vanderbilt University Medical Center, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huirong","family":"Xie","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences, The Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ako","family":"Kodama","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Osuga","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Ustunel","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, School of Medicine, Akdeniz University, Antalya 07070, Turkey; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Research Center, Vanderbilt University Medical Center, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Caprioli","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Research Center, Vanderbilt University Medical Center, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takiko","family":"Daikoku","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences, The Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhansu K.","family":"Dey","sequence":"additional","affiliation":[{"name":"Division of Reproductive Sciences, The Perinatal 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