Embryonic catch-up growth after exposure to the ketone body D,L,-beta-hydroxybutyrate in vitro.
The capability of rodent embryos to recover in growth and development subsequent to exposure to an insult was investigated employing whole embryo culture. Early somite stage mouse embryos were exposed to 32 mM D,L,-beta-hydroxybutyrate (D,L,-beta OHB) for 24 hr (Period I), and were then transferred and maintained in control medium for an additional 36 hr maximum (Period II). Growth of this recovery group (Group B) was monitored at various time points of Period II and the results were compared with an unexposed control group (Group A) and another continuously-exposed reference group (Group C). At the end of Period I, 100% of D,L,-beta OHB-exposed embryos exhibited neural tube closure defects and were growth retarded. At 36 hr of Period II, cranial and caudal neural tube defects of Group B embryos were reduced to 3-7% and 0%, respectively. These embryos also demonstrated an excess in growth velocity during recovery so that at the end of Period II, total protein content was comparable to control values. In contrast, Group C embryos remained growth retarded and showed a significant increase in cranial and caudal neural tube defects (20 and 75%, respectively). Thus, neurulating mouse embryos were capable of catch-up growth following an embryotoxic exposure to D,L,-beta OHB. The progression of development of total protein values and morphological features such as elimination of neural tube defects was intimately related to the amount of time allowed for recovery. Moreover, an elevation of growth rate over normality, which is characteristic of catch-up growth, was observed.
Shum
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Department of Cell Biology and Anatomy, School of Medicine, University of North Carolina, Chapel Hill 27599-7090.
Sadler
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D020155:3-Hydroxybutyric Acid; D000818:Animals; D004622:Embryo, Mammalian / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D006885:Hydroxybutyrates / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D008855:Microscopy, Electron, Scanning; D012016:Reference Values; D013723:Teratogens / Q000633:toxicity*
D006885:Hydroxybutyrates; D013723:Teratogens; D020155:3-Hydroxybutyric Acid