title: Recovery by mouse embryos following teratogenic exposure to ketosis.
abstract: Previous studies have shown that the ketone body D,L,-beta-hydroxybutyrate was teratogenic to mouse embryos exposed in culture during the period of neurulation. Inhibition of closure of the cranial and caudal neuropores was the most frequently occurring defect and these abnormalities were thought to be the forerunner of anencephaly and spina bifida, respectively. However, additional studies demonstrated that embryos could recover morphologically from these effects if the ketone body was removed from the culture medium and if the recovery period was of sufficient duration. In an attempt to define further the phenomenon responsible for this recovery and to determine the extent of the recovery process, the present study examining the cross-sectional area, cell number, and mitotic index of cranial neuroepithelial cells was conducted in mouse embryos cultured from the early somite stage under one of the following conditions: 1) control medium for 60 h; 2) medium containing 32 mmol/l D,L,-beta-hydroxybutyrate for 24 h followed by culture in control medium for an additional 36 h (recovery group); 3) medium containing 32 mmol/l D,L,-beta-hydroxybutyrate for 60 h (continuously exposed group). The results indicate that although neural tube closure occurred in the recovery group, complete recovery was limited to the ventral regions of the forebrain and that the remainder of the prosencephalon as well as the rhombencephalon failed to undergo complete catch-up growth. Thus, cell numbers in these areas were approximately 70% of control values. Therefore, while the gross anatomical disturbances produced by the ketone body may be compensated for, histological alterations in the affected tissues remain. Ultimately, these data suggest that neurological deficits may be an outcome of ketone body exposure during the early stages of embryogenesis.
authors.affiliation: Department of Cell Biology and Anatomy, School of Medicine, University of North Carolina, Chapel Hill.
authors.forename: L
authors.initials: L
authors.lastname: Shum
authors.forename: T W
authors.initials: TW
authors.lastname: Sadler
mesh_terms: D020155:3-Hydroxybutyric Acid; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D004475:Ectoderm / Q000187:drug effects / Q000648:ultrastructure; D004622:Embryo, Mammalian / Q000187:drug effects / Q000648:ultrastructure*; D005260:Female; D006885:Hydroxybutyrates / Q000633:toxicity*; D007662:Ketosis / Q000196:embryology / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008813:Mice, Inbred ICR; D008855:Microscopy, Electron, Scanning; D008940:Mitotic Index; D009924:Organ Culture Techniques; D011247:Pregnancy; D013723:Teratogens
chemical_list: D006885:Hydroxybutyrates; D013723:Teratogens; D020155:3-Hydroxybutyric Acid