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Suppression of erythroid cell differentiation in mouse embryos exposed to retinoic acid in utero
Y Yasuda1, H Konishi, T Matsuo
1Department of Anatomy (1st Division), Kinki University School of Medicine, Osaka, Japan.
Abstract:
Differentiation of circulating erythrocytes was inhibited by all-trans-retinoic acid in 8- and 9-day-old mouse embryos exposed in utero on day 8 of gestation. Histochemical, light, and electron microscopic examinations revealed that all-trans-retinoic acid first decreased the numbers of polychromatic erythroblasts and then increased them. Simultaneously, immature erythroblasts proliferated, and differentiation of mature primitive erythrocytes was suppressed. Electron microscopy of these immature erythroblasts revealed monosomes rather than the usual polyribosomes in the cytoplasm. RNA histochemistry revealed a greater number of intermediate differentiating erythroblasts with pyronin-positive cytoplasm than those in the controls and revealed also a dose-dependent relationship between the number of polychromatic erythroblasts with positive pyronin staining and the controls. These findings suggest that all-trans-retinoic acid destroys the messenger RNA system, resulting in an inability to produce hemoglobin.
Insights
All-trans-retinoic acid exposure in pregnant mice disrupts red blood cell development by damaging messenger RNA, hindering hemoglobin production in developing embryos.
Area of Science:
- Developmental Biology
- Hematology
- Toxicology
Background:
- Erythropoiesis is a complex process crucial for oxygen transport.
- Retinoids play vital roles in embryonic development.
- Understanding teratogenic effects of compounds is essential for risk assessment.
Purpose of the Study:
- To investigate the effects of all-trans-retinoic acid on embryonic erythropoiesis.
- To elucidate the molecular mechanisms underlying retinoic acid-induced developmental toxicity.
Main Methods:
- In utero exposure of mouse embryos to all-trans-retinoic acid on day 8 of gestation.
- Histochemical, light, and electron microscopy for cellular analysis.
- RNA histochemistry to assess messenger RNA integrity.
Main Results:
- All-trans-retinoic acid inhibited erythrocyte differentiation.
- Observed proliferation of immature erythroblasts and suppression of mature erythrocyte formation.
- Evidence of messenger RNA damage, indicated by monosomes and pyronin-positive staining, in differentiating erythroblasts.
Conclusions:
- All-trans-retinoic acid disrupts embryonic erythropoiesis by targeting the messenger RNA system.
- This disruption leads to impaired hemoglobin synthesis and potential developmental abnormalities.
- The findings highlight a critical period of vulnerability during early embryonic development to retinoid toxicity.