吡咯西啶双烷生物碱暴露对生长发育迟缓胎鼠肾上腺皮质酮合成功能的影响

Objectives: to investigate the pyrrolizidine alkaloids (PAs)-induced developmental toxicities from the perspective of adrenal steroidogenic function. Methods: Pregnant mice were administered with monocrotaline (Mct) or retrorsine (Ret) during second and third trimesters. The fetuses were weighed. The level of corticosterone (CORT) in maternal and fetal serum as well as fetal adrenocorticotropic hormone (ACTH) were detected. The expression of placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), adrenal cytochrome P450 (CYP) 11A1 and steroidogenic acute regulatory protein (StAR) as well as CYP3A16 were measured. Results: When compared with control, Mct and Ret significantly reduced the fetal body weight (P<0.01, P<0.05) while elevated the fetal CORT level (P<0.05). The level of maternal serum CORT in Mct group had an increased tendency that the expression of placental 11?-HSD-2 was likely to be decreased. For Ret group, the 11?-HSD-2 mRNA expression had an increased tendency while both adrenal CYP11A1 and StAR expression showed elevated tendency or significant increasing (P<0.05). Both two PAs are able to decrease the expression of adrenal CYP3A16, especially for Mct (P<0.05). Conclusion: Prenatal PAs (Mct or Ret) ingestion could lead to developmental toxicities in mice, the common potential mechanism might be attributed to increased level of serum CORT in fetus. Mct could result in fetal over-exposure to maternal CORT while Ret might intensify the adrenal steroidgenesis via affecting StAR expression.