{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:14:36Z","timestamp":1790856876937,"version":"4.1.0"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008503","name":"Consortia for Improving Medicine with Innovation and Technology","doi-asserted-by":"publisher","award":["W0125"],"award-info":[{"award-number":["W0125"]}],"id":[{"id":"10.13039\/100008503","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Anorectal malformation (ARM) is the most common congenital digestive tract anomaly in newborns, and children with ARM often have varying degrees of underdevelopment of the pelvic floor muscles (PFMs). To explore the effects of Rar\u03b1 (NR1B1) and Pitx2 on the development of rat PFMs, we constructed a rat ARM animal model using all-trans retinoic acid (ATRA), and verified the expression of Rar\u03b1 and Pitx2 in the PFMs of fetal rats. Additionally, we used rat myoblasts (L6 cells) to investigate the regulatory roles of Rar\u03b1 and Pitx2 in skeletal muscle myoblast differentiation and their interactions. The results indicated a significant decrease in the expression of Rar\u03b1 and Pitx2 in the PFMs of fetal rats with ARM. ATRA can also decrease the expression of Rar\u03b1 and Pitx2 in the L6 cells, while affecting the differentiation and fusion of L6 cells. Knocking down Rar\u03b1 in L6 cells reduced the expression of Pitx2, Myod1, Mymk, and decreased myogenic activity in L6 cells. When Rar\u03b1 is activated, the decreased expression of Pitx2, Myod1, and Mymk and myogenic differentiation can be restored to different extents. At the same time, increasing or inhibiting the expression of Pitx2 can counteract the effects of knocking down Rar\u03b1 and activating Rar\u03b1 respectively. These results indicate that Pitx2 may be downstream of the transcription factor Rar\u03b1, mediating the effects of ATRA on the development of fetal rat PFMs.<\/jats:p>","DOI":"10.1371\/journal.pone.0345764","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T17:32:37Z","timestamp":1776447157000},"page":"e0345764","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["ATRA influences the differentiation and fusion of myoblasts by regulating Rar\u03b1\/Pitx2, leading to abnormal development of the pelvic floor muscles (PFMs) in fetal 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