{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:25:54Z","timestamp":1698971154499},"reference-count":24,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100018916","name":"Suzhou Municipal Health Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018916","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Bladder dysfunction has been linked to the progression of renal failure in children with neurogenic bladder (NB) dysfunction. The purpose of this study was to determine whether bladder injuries in fetal rats with myelomeningocele (MMC) may be treated with folic acid.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pregnant Sprague\u2010Dawley rats were randomly divided into three groups. On the 10th day of gestation, pregnant rats were intragastrically injected with all\u2010trans retinoic acid (ATRA) (60\u2009mg\/kg) to induce MMC fetal rats. The same amount of olive oil was put into the control group to create normal fetal rats. The rats in the rescue group were given folic acid (40\u2009mg\/kg) by gavage 0.5 and 12\u2009hr after ATRA therapy. Bladders were obtained via cesarean section on embryonic day E20.5 and examined for MMC. The histology of the fetuses was examined using hematoxylin and eosin staining, and immunohistochemistry (IHC) was utilized to determine the expression of \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) and neuron\u2010specific nuclear\u2010binding protein (NeuN). Furthermore, the levels of neuromuscular development\u2010related and apoptotic proteins were determined by western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The incidence of MMC in the model group was 60.6% (20\/33) while it was much lower in the rescue group (21.4%). In comparison to the model group, the weight and crown\u2010rump length of the fetal rats in the rescue group were significantly improved. IHC revealed that there was no significant difference in the expression of \u03b1\u2010SMA and NeuN between the control and ATRA groups, while the expression levels decreased significantly in the MMC group. Western blot analysis showed that there was no significant difference between the model and ATRA groups, but the expression of the \u03b1\u2010SMA protein and the \u03b23\u2010tubulin was much lower in the MMC group than in the control group. After the administration of folic acid, the \u03b1\u2010SMA and \u03b23\u2010tubulin proteins considerably increased in the folic acid\u2010rescued MMC group and folic acid\u2010rescued ATRA group. Meanwhile, in the control group, the expression of cleaved caspase\u20103 in the bladder tissue was significantly higher, and the expression of poly (ADP\u2010ribose) polymerase (PARP) protein was significantly lower compared to the control group. Folic acid therapy reduced cleaved caspase\u20103 expression while increasing PARP expression in comparison to the MMC group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NB in MMC fetal rats is associated with the reduction of bladder nerve and smooth muscle\u2010related protein synthesis. However, folic acid therapy can help improve these functional deficiencies. Folic acid also exhibits strong anti\u2010apoptotic properties against NB in MMC fetal rats.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2243","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T10:20:23Z","timestamp":1693822823000},"page":"1685-1692","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Folic acid supplementation rescues bladder injury in fetal rats with myelomeningocele"],"prefix":"10.1002","volume":"115","author":[{"given":"Shaoguang","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Urology Children's Hospital of Soochow University  Suzhou Jiangsu People's Republic of China"},{"name":"Department of Pediatric Surgery Hangzhou Children's Hospital  Hangzhou People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yicheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology Children's Hospital of Soochow University  Suzhou Jiangsu People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhechen","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Urology Children's Hospital of Soochow University  Suzhou Jiangsu People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunli","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Urology Children's Hospital of Soochow University  Suzhou Jiangsu People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3945\/an.112.003392"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu5114760"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00001.2006"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.518"},{"issue":"10","key":"e_1_2_10_6_1","first-page":"820","article-title":"Mitochondrial modulation of apoptosis induced by low\u2010dose radiation in mouse testicular cells","volume":"26","author":"Fang F.","year":"2013","journal-title":"Biomedical and Environmental 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