Ossification of the rat and mouse skeleton in the perinatal period
TL;DR: A reduced rate of ossification at a given time of development, which is never less within the normal range, may be indicative of a nonspecific retardation of fetal maturation.
Abstract: In the perinatal period the skeletal development of rats and mice showed transient stages of missing to incomplete or largely complete ossification. Alizarin red S staining revealed characteristic morphological patterns of maturation, which differed from one part of the skeleton to another. In the two species examined all the skeletal elements were ossified 2 days after birth. In about 12% of the rats and 90% of the mice an additional sternebra formed in the postnatal period. In a small number of cases abnormal ossification was observed. A few days after term the spontaneous rate of abnormally ossified bones was found to be 0.51% in the rats and 1.40% in the mice. A reduced rate of ossification at a given time of development which is never less within the normal range, may be indicative of a nonspecific retardation of fetal maturation.
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TL;DR: The possibility exists that extra 14th ribs could be regarded as indicators of teratogenic potency of a drug at some higher dosage; but the data presented did not demonstrate the usefulness of the other skeletal variants examined as signals ofTeratogenic potential.
Abstract: Skeletal variations were studied in 20-day rat fetuses from pregnant females given acetazolamide, actinomycin D, or sodium salicylate and in vehicle-treated and untreated controls. A slight increase over untreated control values as regards resorptions, malformations, and certain skeletal variants was noted in some vehicle-treated groups. Supernumerary 14th ribs were designated as rudimentary (less than half the length of the 13th rib) or extra (half or greater than half the length of the 13th rib) on the basis of actual measurement showing a bimodal distribution in length. The occurrence of rudimentary 14th ribs was highly variable after vehicle or teratogen treatment. Extra 14th ribs occurred in a dose-related fashion after actinomycin D (days 7 and 9) and sodium salicylate (which sometimes also produced 15th ribs), but not after acetazolamide treatment. Sternebrae were variable in form after most treatments and these changes showed a slight but insignificant increase after actinomycin D or sodium salicylate on day 9. The incidence of variations of vertebral centra was highly changeable after all treatments but was consistently greater after sc treatment with water or acetazolamide and appeared to be dose related after sodium salicylate. The authors believe that none of these skeletal variants should in themselves be considered as malformations. The possibility exists that extra 14th ribs could be regarded as indicators of teratogenic potency of a drug at some higher dosage; but the data presented did not demonstrate the usefulness of the other skeletal variants examined as signals of teratogenic potential.
206 citations
TL;DR: The stage of skeletal ossification in day-21 fetuses is proposed to be used in teratogenic studies in the rat to evaluate retarded fetal development.
Abstract: In teratogenic studies toxic effects may manifest themselves in retarded fetal development, such as a reduction in fetal weight. In searching for an additional index, the number of centers of ossification in seven skeletal districts (sternum, metacarpus, metatarsus, cervical and caudal vertebrae, anterior and posterior proximal phalanges) of rat fetuses delivered on days 19, 20 and 21 of gestation were counted and compared. Results showed uneven ossification in day-19 and -20 fetuses, but sufficiently advanced, homogeneous and uniform ossification in day-21 fetuses to provide a reliable quantitative index for evaluating retarded fetal development. It is therefore proposed that the stage of skeletal ossification in day-21 fetuses be used in teratogenic studies in the rat to evaluate retarded fetal development.
197 citations
TL;DR: A requirement for specially designed studies exists in order to determine the true nature of aberrations and their effects on postnatal development, only then will it be possible to establish a scientific basis for using animal data to estimate human safety.
143 citations
TL;DR: It is concluded from these studies that the heart and the diaphragm are the target organs in nitrofen-induced neonatal death.
137 citations
TL;DR: Oral administration of 200-800 mg/kg VPA (5-20x human therapeutic dose) from Gestational Days (GD) 8 to 17 resulted in increasing maternal toxicity at the higher doses with 100% maternal lethality at 800mg/kg.
127 citations
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TL;DR: A selective, progressive method for staining the skeleton in cleared specimens, developed with rat material, depends on obtaining the proper degree of clearing before staining.
Abstract: A selective, progressive method for staining the skeleton in cleared specimens, developed with rat material.Fix in 95% alcohol for at least 48 to 96 hrs. Even longer fixation is desirable. Then place in a 1% solution of KOH until the bones are clearly visible through the surrounding tissues. Transfer directly to a dilute solution of alizarin in KOH, one part alizarin to 10,000 parts of 1% KOH. Allow the stain to act until the desired intensity is attained. Fresh stain may be added if necessary.Complete the clearing process, (1) in Mall's solution, water 79 parts, glycerine 20 parts and KOH 1 part; (2) in increased concentrations of glycerine. Store in pure glycerine.The success of the method depends on obtaining the proper degree of clearing before staining. If the specimen is insufficiently cleared, a general staining of all tissues usually occurs.
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