{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:35:54Z","timestamp":1791196554223,"version":"4.1.0"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"3","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,1,30]]},"abstract":"<jats:p>\n                    The implantation of a blastocyst into a receptive uterus is\n associated with a series of events, namely the attachment reaction\n followed by decidualization of the stroma. Previous studies established\n that the gene encoding heparin-binding EGF-like growth factor (HB-EGF)\n is expressed in the luminal epithelium solely at the site of blastocyst\n apposition preceding the attachment reaction. We report here the\n expression during implantation of 21 genes encoding other signaling\n proteins, including those belonging to the Bone morphogenetic protein\n (BMP), fibroblast growth factor (FGF), WNT, and Hedgehog (HH) pathways.\n We find that the attachment reaction is associated with a localized\n stromal induction of genes encoding BMP-2, FGF-2, and WNT-4. Despite\n efforts by many investigators, a simple\n                    <jats:italic>in vitro<\/jats:italic>\n                    model\n of implantation is not yet available to study either the hierarchy of\n the events triggered in the uterus by the embryo or the function of\n individual signaling proteins. We have therefore approached these\n questions by introducing beads loaded with purified factors into the\n receptive uterus. We show that beads soaked in HB-EGF or insulin-like\n growth factor-1 (IGF-1), but not other proteins, induce many of the\n same discrete local responses elicited by the blastocyst, including\n increased localized vascular permeability, decidualization, and\n expression of\n                    <jats:italic>Bmp2<\/jats:italic>\n                    at the sites of the beads. By\n contrast, the expression domains of\n                    <jats:italic>Indian hedgehog<\/jats:italic>\n                    (\n                    <jats:italic>Ihh<\/jats:italic>\n                    ),\n                    <jats:italic>patched<\/jats:italic>\n                    , and\n                    <jats:italic>noggin<\/jats:italic>\n                    become restricted as decidualization proceeds. Significantly, beads\n containing BMP-2 do not themselves elicit an implantation response but\n affect the spacing of implantation sites induced by blastocysts\n cotransferred with the beads.\n                  <\/jats:p>","DOI":"10.1073\/pnas.98.3.1047","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:36:44Z","timestamp":1027679804000},"page":"1047-1052","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":304,"title":["Cellular and molecular responses of the uterus to embryo implantation can be elicited by locally applied growth factors"],"prefix":"10.1073","volume":"98","author":[{"given":"Bibhash C.","family":"Paria","sequence":"first","affiliation":[{"name":"Departments of Pediatrics, Molecular and Integrative\r Physiology, and Obstetrics and Gynecology, University of\r Kansas Medical Center, Ralph L. Smith Research Center, Kansas City,\r KS 66160-7338; and Howard Hughes Medical Institute and\r Department of Cell Biology, Vanderbilt Medical School, Nashville,\r TN 37232-2175"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-ge","family":"Ma","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Molecular and Integrative\r Physiology, and Obstetrics and Gynecology, University of\r Kansas Medical Center, Ralph L. Smith Research Center, Kansas City,\r KS 66160-7338; and Howard Hughes Medical Institute and\r Department of Cell Biology, Vanderbilt Medical School, Nashville,\r TN 37232-2175"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Tan","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Molecular and Integrative\r Physiology, and Obstetrics and Gynecology, University of\r Kansas Medical Center, Ralph L. Smith Research Center, Kansas City,\r KS 66160-7338; and Howard Hughes Medical Institute and\r Department of Cell Biology, Vanderbilt Medical School, Nashville,\r TN 37232-2175"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shefali","family":"Raja","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Molecular and Integrative\r Physiology, and Obstetrics and Gynecology, University of\r Kansas Medical Center, Ralph L. Smith Research Center, Kansas City,\r KS 66160-7338; and Howard Hughes Medical Institute and\r Department of Cell Biology, Vanderbilt Medical School, Nashville,\r TN 37232-2175"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonjoy K.","family":"Das","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Molecular and Integrative\r Physiology, and Obstetrics and Gynecology, University of\r Kansas Medical Center, Ralph L. Smith Research Center, Kansas City,\r KS 66160-7338; and Howard Hughes Medical Institute and\r Department of Cell Biology, Vanderbilt Medical School, Nashville,\r TN 37232-2175"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhansu K.","family":"Dey","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Molecular and Integrative\r Physiology, and Obstetrics and Gynecology, University of\r Kansas Medical Center, Ralph L. Smith Research Center, Kansas City,\r KS 66160-7338; and Howard Hughes Medical Institute and\r Department of Cell Biology, Vanderbilt Medical School, Nashville,\r TN 37232-2175"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigid L. M.","family":"Hogan","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Molecular and Integrative\r Physiology, and Obstetrics and Gynecology, University of\r Kansas Medical Center, Ralph L. Smith Research Center, Kansas City,\r KS 66160-7338; and Howard Hughes Medical Institute and\r Department of Cell Biology, Vanderbilt Medical School, Nashville,\r TN 37232-2175"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,1,30]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1016228"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9767"},{"key":"e_1_3_3_3_2","first-page":"421","volume-title":"Reproductive Endocrinology, Surgery and Technology","author":"Dey S K","year":"1996","unstructured":"S K Dey Reproductive Endocrinology, Surgery and Technology, eds E Y Adashi, J A Rock, Z Rosenwaks (Lippincot\u2013Raven, New York), pp. 421\u2013434 (1996)."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.120.5.1071"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.12.6386"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.1.33"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0130259"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0890735"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-0436.1986.tb00555.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(79)90289-6"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(80)90365-6"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122.9.2687"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod56.5.1097"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0160107"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80402-X"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.12.1561"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod46.2.208"},{"key":"e_1_3_3_18_2","first-page":"903","volume":"10","author":"Barker J","year":"1996","unstructured":"J Barker, M P Hardy, J Zhou, C Bondy, F Lupu, A R Bellve, A Efstratiadis Mol Endocrinol 10, 903\u2013918 (1996).","journal-title":"Mol Endocrinol"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.13.1580"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.13.3505"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.6.627"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.21.10159"},{"key":"e_1_3_3_23_2","first-page":"373","volume-title":"Manipulating the Mouse Embryo, a Laboratory Manual (Section H)","author":"Hogan B L M","year":"1994","unstructured":"B L M Hogan, R Beddington, F Costantini, E Lacy Manipulating the Mouse Embryo, a Laboratory Manual (Section H) (Cold Spring Harbor Lab. 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