{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:51:31Z","timestamp":1761216691467},"reference-count":0,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,7,7]],"date-time":"2008-07-07T00:00:00Z","timestamp":1215388800000},"content-version":"vor","delay-in-days":2501,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2001,9]]},"abstract":"<jats:p>PROBLEM<jats:italic>:<\/jats:italic> Impaired trophoblast invasion during the first trimester of pregnancy is linked to spontaneous abortion, and defective invasion in the second trimester to hypertension+proteinuria (pre\u2010eclampsia). Hypertension developing during the third trimester of human pregnancy represents, in part, a corrective response in the mother to provide adequate placental perfusion for fetal growth when trophoblast has not to invaded and converted the myometrial porprtion of maternal spiral arteries into to low resistance\u2010high capacitance conduits. Deportation of vesicles from hypoxemic trophoblast is thought to cause hypertension plus proteinuria, vascular damage and a systemic coagulopathy. Trophoblast invasion may be inhibited by local cytokines, such as TGF\u2010\u03b2s but Th1\u2010type cytokines associated with pre\u2010eclapmsia and spontaneous abortions (e.g., IL\u20101, TNF\u2010\u03b1, IFN\u2010\u03b3) are not known to inhibit migration at <jats:italic>in situ<\/jats:italic> concentrations. Trophoblast invasion is also inhibited by the binding of surface integrins to fibronectin and fibrin, and fibrin production is stimulated by these Th1 cytokines via up\u2010regulation of prothrombinases(s) such as fgl2 which directly and via TNF\u2010\u03b1\u2010facilitated inflamation compromise trophoblast cell integrity. We, therefore, asked if fgl2 expression and TNF\u2010\u03b1 are increased in first trimester human miscarriage and in third trimester pre\u2010eclampsia.\u2028\nMETHODS: fgl2 mRNA was detected using <jats:italic>in situ<\/jats:italic> hybridization and fgl2 protein by immunohistochemistry. TNF\u2010\u03b1 mRNA and protein were similarly tested. The techniques were validated using uterine sections from day 8.5 of CBA\u00d7DBA\/2 pregnancies, and then were applied to sections of placentae from normal and pre\u2010eclamptic pregnancies with and without intrauterine fetal growth restriction (IUGR). Fibrin was detectectd by immunohistochemistry.\u2028 RESULTS: Expression of fgl2 protein correlated with fgl2 mRNA expression in mouse uteri and in placentae from normal human pregnancies. Increased expression of fgl2 and TNF\u2010\u03b1 mRNA and protein, and increased fibrin deposition was detected in placental trophoblast.\u2028 CONCLUSIONS: Activation of fgl2 prothrombinase by Th1\u2010type cytokines in pregnancy may lead to spontaneous abortion, or in ongoing pregnancy, to pre\u2010eclampsia and\/or IUGR.<\/jats:p>","DOI":"10.1034\/j.1600-0897.2001.d01-3.x","type":"journal-article","created":{"date-parts":[[2003,10,15]],"date-time":"2003-10-15T02:30:22Z","timestamp":1066185022000},"page":"196-210","source":"Crossref","is-referenced-by-count":44,"title":["Activation of the Novel Prothrombinase, fgl2, as a Basis for the Pregnancy Complications Spontaneous Abortion and Pre\u2010eclampsia"],"prefix":"10.1111","volume":"46","author":[{"given":"M.","family":"KNACKSTEDT","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.W.","family":"DING","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.M.","family":"GORCZYNSKI","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.A.","family":"LEVY","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.A.","family":"CLARK","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"KNACKSTEDT","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.C.","family":"ARCK","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"HERTWIG","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.W.","family":"DUDENHAUSEN","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.B.","family":"COULAM","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"AUGUST","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"LEA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.A.","family":"CLARK","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.W.","family":"DING","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,7,7]]},"container-title":["American Journal of Reproductive Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1034%2Fj.1600-0897.2001.d01-3.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1034%2Fj.1600-0897.2001.d01-3.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1034\/j.1600-0897.2001.d01-3.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T16:09:01Z","timestamp":1700410141000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1034\/j.1600-0897.2001.d01-3.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,9]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2001,9]]}},"alternative-id":["10.1034\/j.1600-0897.2001.d01-3.x"],"URL":"https:\/\/doi.org\/10.1034\/j.1600-0897.2001.d01-3.x","archive":["Portico"],"relation":{},"ISSN":["1046-7408","1600-0897"],"issn-type":[{"value":"1046-7408","type":"print"},{"value":"1600-0897","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,9]]}}}