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Notable sequential alterations in notochord volume during development in the Adriamycin rat model
Alan Mortell1, John Gillick, Shay Giles
1Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin 12, Ireland.
Journal of Pediatric Surgery
|March 8, 2005
Summary
Adriamycin exposure causes notochord hypertrophy in rat embryos, significantly increasing notochord volume relative to embryo size. This enlargement is most pronounced around embryonic day 11.
Area of Science:
- Developmental biology
- Teratology
- Morphogenesis
Background:
- The Adriamycin rat model (ARM) is used to study congenital malformations.
- Adriamycin is known to induce abnormal notochord morphology in the foregut region.
Purpose of the Study:
- To sequentially assess notochord volume from embryonic days 10-14 in the ARM.
- To test the hypothesis that notochord hypertrophy peaks shortly after Adriamycin administration.
Main Methods:
- Pregnant rats received Adriamycin or saline on embryonic days 7-9.
- Embryos were collected from E10 to E14 for quantitative morphological analysis.
- The Cavalieri technique was used to determine total embryo and notochord volume.
Main Results:
- Adriamycin-treated embryos showed significantly increased notochord volume from E10-E14 compared to controls.
- The relative notochord volume increase was maximal at embryonic day 11.
- P < .05 indicated statistical significance.
Conclusions:
- Adriamycin administration leads to notochord hypertrophy, with maximal volume increase by E11.
- Increased notochord volume during critical development may disrupt organogenesis.
- This may contribute to the observed vertebral, anorectal, cardiac, tracheoesophageal, renal, and limb malformations in the ARM.