{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T15:45:43Z","timestamp":1792424743905,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2010,5,24]],"date-time":"2010-05-24T00:00:00Z","timestamp":1274659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND:<\/jats:bold> Isolated epispadias is the mildest phenotype of the exstrophy\u2010epispadias complex, a urogenital birth defect of variable severity. The androgen receptor antagonist flutamide (FLU) is known to cause malformations in the rat genital and reproductive tract, and single\u2010dose prenatal FLU exposure can induce epispadias in rat offspring. The <jats:italic>Cyr61<\/jats:italic> gene exhibited the highest response to FLU in rat fetal testis, and we suggested it a promising candidate gene for epispadias in humans, because its protein product promotes proliferation, migration, and adhesion of endothelial cells and fibroblasts. <jats:bold>METHODS:<\/jats:bold> We used whole mount in situ analysis in mice to investigate ventrocaudal expression of the <jats:italic>Cyr61<\/jats:italic> transcript at gestational days 9.5 to 11.5, which is the equivalent of human gestational weeks 4 to 6 (postulated time of epispadias organogenesis in humans). We also performed mutational analysis of the <jats:italic>CYR61<\/jats:italic> gene in 11 patients with isolated epispadias and in additional eight patients with the related classic bladder exstrophy phenotype. <jats:bold>RESULTS:<\/jats:bold> Expression of <jats:italic>Cyr61<\/jats:italic> was detected in endothelial cells of vessels surrounding the cloaca and the umbilical cord on gestational days 10 and 11.5. The mutation screening, however, revealed no alterations in the coding region of human <jats:italic>CYR61<\/jats:italic>. <jats:bold>CONCLUSIONS:<\/jats:bold> The spatiotemporal expression pattern observed suggests a role for <jats:italic>Cyr61<\/jats:italic> in the development of the external genitalia. Our mutation screening study, however, could not confirm that mutations affecting the <jats:italic>CYR61<\/jats:italic> gene are a frequent cause of epispadias or classic bladder exstrophy, although rare mutations might be detectable in larger patient samples. Birth Defects Research (Part A), 2010. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdra.20668","type":"journal-article","created":{"date-parts":[[2010,5,27]],"date-time":"2010-05-27T01:07:49Z","timestamp":1274922469000},"page":"546-550","source":"Crossref","is-referenced-by-count":5,"title":["Embryonic expression of the cysteine rich protein 61 (<i>CYR61<\/i>) gene: A candidate for the development of human 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