PMID- 31787253 OWN - NLM STAT- MEDLINE DCOM- 20200924 LR - 20200924 IS - 1618-0372 (Electronic) IS - 0065-1281 (Linking) VI - 122 IP - 1 DP - 2020 Jan TI - Involvement of proliferative and apoptotic factors in the development of hindgut in rat fetuses with ethylenethiourea-induced anorectal malformations. PG - 151466 LID - S0065-1281(19)30452-0 [pii] LID - 10.1016/j.acthis.2019.151466 [doi] AB - BACKGROUND: Anorectal malformations (ARMs) are common congenital malformations of the terminal digestive tract, but little is known regarding their pathogenesis. Aberrant cell proliferation/apoptosis are believed to be involved in ARMs. However, there are no studies on proliferation/apoptosis-related genes. PURPOSE: We aimed to investigate the spatiotemporal expression patterns of two proliferation/apoptosis-related genes (MYC proto-oncogene and tumor protein p53) and explore their potential functions in the hindguts of ethylene thiourea-induced ARMs rat fetuses. METHODS: MYC and p53 expression was evaluated using immunohistochemical staining, western blotting, and quantitative real-time polymerase chain reaction (RT-qPCR). Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and p53 costaining were performed to assay the colocalization of apoptotic and p53-expressing cells. RESULTS: Rat fetuses with ARMs displayed fusion failure of the urogenital septum and cloacal membrane. In the control group, MYC was persistently expressed from gestational day (GD)14 to GD16 and distributed throughout the hindgut, while p53 was weakly detected in the terminal segment of the urethra and hindgut; in the ARMs group, MYC expression was obviously reduced, while p53 was widely and highly expressed in the urethra and hindgut. Western blotting and RT-qPCR confirmed the decrease in MYC and increase in p53 expression in ARMs. TUNEL and p53 co-staining revealed considerable overlap between apoptotic and p53-expressing cells. CONCLUSION: The expression patterns of c-myc and p53 were disrupted in ARMs rat embryos, and the downregulation of c-myc and upregulation of p53 might be related to the development of ARMs at the key time points of ARMs morphogenesis. CI - Copyright (c) 2019 The Authors. Published by Elsevier GmbH.. All rights reserved. FAU - Long, Caiyun AU - Long C AD - Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, PR China. FAU - Xiao, Yunxia AU - Xiao Y AD - Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, PR China. FAU - Li, Siying AU - Li S AD - Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, PR China. FAU - Tang, Xiaobing AU - Tang X AD - Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, PR China. FAU - Yuan, Zhengwei AU - Yuan Z AD - The Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, PR China. FAU - Bai, Yuzuo AU - Bai Y AD - Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, PR China. Electronic address: baiyz1216@126.com. LA - eng PT - Journal Article DEP - 20191128 PL - Germany TA - Acta Histochem JT - Acta histochemica JID - 0370320 RN - 0 (Proto-Oncogene Proteins c-myc) RN - 0 (Tp53 protein, rat) RN - 0 (Tumor Suppressor Protein p53) RN - 24FOJ4N18S (Ethylenethiourea) SB - IM MH - Animals MH - *Anorectal Malformations/chemically induced/embryology/pathology MH - Apoptosis/drug effects MH - Cell Proliferation/drug effects MH - Ethylenethiourea/*toxicity MH - Female MH - *Fetus/embryology/pathology MH - Gene Expression Regulation, Developmental/*drug effects MH - *Intestines/embryology/pathology MH - Pregnancy MH - Proto-Oncogene Proteins c-myc/*biosynthesis MH - Rats MH - Rats, Wistar MH - Tumor Suppressor Protein p53/*biosynthesis OTO - NOTNLM OT - Anorectal malformations OT - Development OT - Hindgut OT - Rat OT - c-myc OT - p53 EDAT- 2019/12/04 06:00 MHDA- 2020/09/25 06:00 CRDT- 2019/12/03 06:00 PHST- 2019/07/13 00:00 [received] PHST- 2019/10/16 00:00 [revised] PHST- 2019/11/14 00:00 [accepted] PHST- 2019/12/04 06:00 [pubmed] PHST- 2020/09/25 06:00 [medline] PHST- 2019/12/03 06:00 [entrez] AID - S0065-1281(19)30452-0 [pii] AID - 10.1016/j.acthis.2019.151466 [doi] PST - ppublish SO - Acta Histochem. 2020 Jan;122(1):151466. doi: 10.1016/j.acthis.2019.151466. Epub 2019 Nov 28.