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Deleterious effects of prenatal prednisolone exposure upon morphological and behavioral development of mice
Insights
Prenatal exposure to prednisolone (PRED) in mice caused reduced birth weight and delayed development in female offspring. However, reproductive capabilities remained unaffected, suggesting PRED impacts somatic and motor development.
Area of Science:
- Endocrinology
- Developmental Biology
- Reproductive Science
Background:
- Prenatal exposure to synthetic glucocorticoids can impact fetal development.
- Prednisolone (PRED) is a commonly used synthetic glucocorticoid with potential teratogenic effects.
- Understanding the specific effects of PRED on fetal development is crucial for risk assessment.
Purpose of the Study:
- To investigate the influence of prenatal prednisolone (PRED) exposure on female mouse offspring.
- To assess the impact of PRED on somatic growth, morphological development, developmental milestones, and reproductive competence.
- To explore the potential mechanism of PRED's action, possibly involving estrogen-binding protein.
Main Methods:
- Female mice were administered prednisolone (PRED) on Days 13-18 of pregnancy.
- Offspring were monitored for birth weight, weaning weight, adult weight, anogenital distance, and developmental milestones (eye opening, lifting, walking, gripping).
- Reproductive competence was assessed through pregnancy success, lactation, and fighting behavior. An antiestrogenic compound (MER-25) was used concurrently in some groups.
Main Results:
- Prenatal PRED exposure significantly reduced offspring weight at birth, weaning, and in adulthood (at higher doses).
- Morphological masculinization (increased anogenital distance) and delayed developmental milestones were observed.
- Concurrent administration of MER-25 prevented the reduction in birth weight, suggesting PRED acts partly via estrogen-binding protein attenuation.
- Reproductive competence was not significantly affected by prenatal PRED exposure.
Conclusions:
- Prenatal exposure to prednisolone (PRED) markedly affects somatic and muscular/motor development in female offspring.
- The findings suggest PRED interferes with normal developmental trajectories, potentially through hormonal pathways.
- Further research into gonadal hormone levels is recommended to fully elucidate the mechanism of PRED's developmental effects.
Abstract:
The influence of prenatal exposure to the synthetic glucocorticoid prednisolone (PRED) was examined in female offspring of mice administered the drug on Days 13-18 of pregnancy. The offspring weighed significantly less than control animals at birth and weaning. Animals born of mothers given the highest dosage of the drug (400 microgram) weighed less than controls in adulthood. Fetal exposure to PRED also resulted in morphological masculinization as evidenced by an increase in anogenital distance. In addition to its marked influence, prenatal PRED exposure retarded the attainment of the developmental milestones of eye opening, lifting, walking, and gripping. The effect of PRED upon the fetus is relatively rapid in that a reduction of fetal weight was observed in 13-day-old conceptae 7.5 hr following a maternal injection of PRED. The administration of an antiestrogenic compound (MER-25) concurrently with PRED prevented the reduction in birth weight, thereby suggesting that PRED acts, in part, by its known attenuation of fetoneonatal estrogen-binding protein. And finally, fetal exposure to PRED had virtually no effect upon reproductive competence as assessed by proportion of successful pregnancies, lactation performance, and postpartum fighting behavior. It is concluded that prenatal exposure to PRED markedly affects somatic and muscular/motor development and it may be worthwhile to examine the influence of the drug upon levels of gonadal hormones in an attempt to elucidate the mechanism through which its effects are produced.