RESUMEN
The relationship between insulin-induced maternal hypoglycemia and teratogenicity was investigated in detail. We injected 4 different forms of insulin (insulin human, aspart, glargine, and detemir) subcutaneously at 1 or 2 dose levels to Sprague-Dawley rats from Days 6 to 11 of pregnancy, measured blood glucose levels, and conducted fetal examination. In the insulin human and aspart (low dose) groups, while severe hypoglycemia (approximately 50mg/dL) was seen, it lasted only 6h and no fetal anomalies were observed. Fetal axial skeleton anomalies were observed in the aspart (high dose) group, which exhibited intermediate-duration of severe hypoglycemia (9h). Eye and axial skeleton anomalies were observed in the glargine and detemir groups, which exhibited continuous severe hypoglycemia (≥9h). These results revealed that insulin-induced maternal hypoglycemia caused fetal eye and skeleton anomalies and the causative key factors were duration of maternal severe hypoglycemia.
Asunto(s)
Anomalías del Ojo/etiología , Hipoglucemia/complicaciones , Esqueleto/anomalías , Animales , Glucemia/análisis , Femenino , Hipoglucemia/sangre , Hipoglucemia/inducido químicamente , Hipoglucemiantes/farmacología , Insulina/farmacología , Masculino , Embarazo , Ratas Sprague-DawleyRESUMEN
ABSTRACT The development of DBA/2J mouse strain embryos is nearly 12 h - or 6 somite pairs - delayed as compared to the outbred NMRI mouse embryos of the same age on gestation days (GD) 8-12. To evaluate inter-strain differences in susceptibility to teratogens, dams were treated with methylnitrosourea (MNU, 5 mg/kg body weight i.p.) on defined gestation days (NMRI: GD 9, 91/2 or 10; DBA/2J: GD 10 or 101/2). Skeletal anomalies produced by MNU on both mouse strains varied with the GD of treatment. The pattern of anomalies produced by MNU on a given GD markedly differed between the two mouse strains, yet they were similar -with a few exceptions- when exposures at equivalent embryonic stages are compared. Findings from this study indicated that strain-dependent differences in the developmental stage of mouse embryos of the same gestational age occur, a possibility that has been often neglected when inter-strain differences in susceptibility to developmental toxicants are interpreted.