Critical timing of bladder embryogenesis in an adriamycin-exposed rat fetal model: a clue to the origin of the bladder.
OBJECTIVE
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.


CONCLUSIONS
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.
Liu
M I
MI
F. Douglas Stephens Surgical Research Laboratory, Royal Children's Hospital Research Institute, Melbourne, Australia.
Hutson
J M
JM
Zhou
B
B
D000818:Animals; D004195:Disease Models, Animal; D004317:Doxorubicin; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013997:Time Factors; D001743:Urinary Bladder / Q000002:abnormalities* / Q000196:embryology*; D014564:Urogenital Abnormalities / Q000139:chemically induced / Q000196:embryology*
D004317:Doxorubicin