Cloacal and urogenital malformations in adriamycin-exposed rat fetuses.
OBJECTIVE
To determine the spectrum of cloacal and urogenital malformations in rat fetuses prenatally exposed to adriamycin, which causes abnormalities that strongly resemble the VATER association (vertebral defects, anal atresia, tracheo-oesophageal fistula with oesophageal atresia, renal defects and radial limb dysplasia) in humans, and to evaluate how closely such anomalies resemble those seen in humans.


METHODS
Timed-pregnant rats were injected intraperitoneally with adriamycin at 6-9 days of gestation; a control group received saline only. Fetuses (35 treated and 30 control) were recovered at 21 days of gestation, and examined macroscopically and microscopically for cloacal and urogenital abnormalities.


RESULTS
All the treated fetuses had no bladders and severe hydroureter/hydronephrosis on one or both sides. Male fetuses had a proximal blind-ending urethra communicating with dilated ureters and giving rise to vasa. Female fetuses had a persistent urogenital sinus communicating with the ureters and cervix/uterus; 57% of the treated group had an imperforate anus and some had recto-urethral fistulae (males) or recto-urogenital fistulae (females).


CONCLUSIONS
Rat fetuses exposed to adriamycin have a spectrum of cloacal and urogenital anomalies (predominantly no bladder) which is more severe than those of the human VATER association. Nonetheless, this is an excellent animal model for the study of genitourinary embryology, especially bladder development.
Liu
M I
MI
F. Douglas Stephens Surgical Research Laboratory, Royal Children's Hospital Research Institute, Melbourne, Australia.
Hutson
J M
JM
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002988:Cloaca / Q000002:abnormalities*; D004317:Doxorubicin / Q000009:adverse effects*; D005260:Female; D008297:Male; D008854:Microscopy, Electron; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014564:Urogenital Abnormalities / Q000139:chemically induced*
D000970:Antineoplastic Agents; D004317:Doxorubicin