PMID- 10591562 OWN - NLM STAT- MEDLINE DCOM- 20000105 LR - 20190710 IS - 0022-3468 (Print) IS - 0022-3468 (Linking) VI - 34 IP - 11 DP - 1999 Nov TI - Critical timing of bladder embryogenesis in an adriamycin-exposed rat fetal model: a clue to the origin of the bladder. PG - 1647-51 AB - BACKGROUND/PURPOSE: Administration of Adriamycin (ADR) in utero to pregnant rats (vaginal plug, day 0) on gestational days (GD) 6 to 9 resulted in the offspring having a cluster of malformations, including absence of bladder in 100% of cases. This study aimed to determine the critical timing of the embryological window in bladder development in this animal model. METHODS: Timed-pregnant rats were divided randomly and injected intraperitoneally with ADR at 2 mg/kg on GD 6 to 9; GD 7 to 10; GD 8 to 11; GD 9 to 12; GD 6,8, and 9 (missing GD 7); and GD 6, 7, and 9 (missing GD 8). The control group received saline. Fetuses were harvested near term on GD 21 and dissected under a dissecting microscope and examined for gross anorectal and urogenital anomalies. RESULTS: Administration of ADR on GD 6 to 9 (n = 63); GD 7 to 10 (n = 42); and GD 6, 7, and 9 (n = 35) resulted in 100%, 83%, and 77% bladder agenesis respectively, in contrast with 53% and 26% on GD 8 to 11 (n = 36) and GD 6, 8, and 9 (n = 49), respectively. The control (n = 52) and the GD 9 to 12 (n = 27) groups all had normal bladder development. The proportion of other urogenital and anorectal anomalies mirror that of bladder agenesis. CONCLUSION: The results showed GD 7 to be the critical embryological timing in which bladder development can be affected by ADR, possibly by targeting the gene that is expressed in the embryonic bladder during this narrow time interval. FAU - Liu, M I AU - Liu MI AD - F. Douglas Stephens Surgical Research Laboratory, Royal Children's Hospital Research Institute, Melbourne, Australia. FAU - Hutson, J M AU - Hutson JM FAU - Zhou, B AU - Zhou B LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Pediatr Surg JT - Journal of pediatric surgery JID - 0052631 RN - 80168379AG (Doxorubicin) SB - IM MH - Animals MH - Disease Models, Animal MH - Doxorubicin MH - Embryonic and Fetal Development/drug effects MH - Female MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley MH - Reference Values MH - Time Factors MH - Urinary Bladder/*abnormalities/*embryology MH - Urogenital Abnormalities/chemically induced/*embryology EDAT- 1999/12/11 00:00 MHDA- 1999/12/11 00:01 CRDT- 1999/12/11 00:00 PHST- 1999/12/11 00:00 [pubmed] PHST- 1999/12/11 00:01 [medline] PHST- 1999/12/11 00:00 [entrez] AID - S0022-3468(99)90636-X [pii] AID - 10.1016/s0022-3468(99)90636-x [doi] PST - ppublish SO - J Pediatr Surg. 1999 Nov;34(11):1647-51. doi: 10.1016/s0022-3468(99)90636-x.