Combined administration of anti-kidney and anti-heart sera induces high rates of cardiovascular malformations in rat embryos, likely due to yolk sac dysfunction from immunological cross-reactivity.
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Does not support clinical translation; hypothesis-generating for immunological mechanisms in congenital malformations.
Wistar rats were administered rabbit anti‐tissue serum alone or in combination with sub‐teratogenic doses of anti‐kidney serum (AKS) on day 9 of gestation. The results showed that the incidence of cardiovascular malformations was highest (46.7%) when a small dose (1 ml/kg) of AKS given on day 9 was followed by 9 ml/kg of anti‐heart serum (AHS) on day 10. The most common cardiovascular malformations were ventricular septal defects associated with aortic arch anomalies. The spectrum of malformations did not vary with the injected sera. Immunodiffusion studies indicated that the kidney, umbilical cord and yolk sac tissues have at least one common antigen. Between the AHS and the kidney antigen, a slight precipitin band was also demonstrated. These results suggest that the synergistic effects of antisera depend on the degree of immunological cross‐reaction with the yolk sac, and that the mechanisms of teratogenicity by the combined administration is caused mainly by yolk sac dysfunction.
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Miyata et al. (1986) studied this question.
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