Oocytes, in general, are greatly enriched in mitochondria to support higher rates of macromolecular synthesis and critical physiological processes characteristic of early development. An inability of these organelles to amplify and/or to accumulate ATP has been linked to developmental abnormality or arrest. The number of mitochondrial genomes present in mature mouse and human metaphase II oocytes was estimated by fluorescent rapid cycle DNA amplification, which is a highly sensitive technique ideally suited to quantitative mitochondrial DNA (mtDNA) analysis in individual cells. A considerable degree of variability was observed between individual samples. An overall average of 1.59 × 105 and 3.14 × 105 mtDNA molecules were detected per mouse and human oocyte, respectively. Furthermore, the mtDNA copy number was examined in polar bodies and contrasted with the concentration in their corresponding oocytes. In addition, the density of mtDNA in a cytoplasmic sample was estimated in an attempt to determine the approximate number of mitochondria transferred during clinical cytoplasmic donation procedures as well as to develop a clinical tool for the assessment and selection of oocytes during in vitro fertilisation procedures. However, no correlation was identified between the mtDNA concentration in either polar bodies or cytoplasmic samples and their corresponding oocyte.

Background: Our objectives were to identify serum marker proteins in rats that might serve as sensitive indicators of hepatomegaly, hepatocellular necrosis, or hepatobiliary injury and to use them to analyze data from a collaborative proteomics project. Methods: In each of 4 studies comprising the collaborative project, rats were given 1 of 4 compounds that target the liver through different mechanisms. Sera and liver samples were collected by terminal bleeds at 1 of 3 postdose time points. Sera were depleted of major secretory proteins and then separated into protein features by 2-dimensional gel electrophoresis (2DGE). Liver specimens were also processed and subjected to 2DGE. Protein spots that significantly increased or decreased in quantity after drug treatment were recovered, digested, analyzed by mass spectroscopy, and compared with available databases for identification. Criteria for further consideration were (a) temporal expression (i.e., increase or decrease at early, fulminant, or recovery periods), (b) known biological function, (c) probable hepatic origin, and (d) any previous association with toxicity in published studies. Markers that changed significantly at the early time point were important because of their potential sensitivity for signaling minimal damage. Results: Vitamin D-binding protein, paraoxonase, cellular retinol-binding protein, malate dehydrogenase, F-protein, and purine nucleoside phosphorylase were

The Executive Committee of the Society of Toxicologic Pathology (STP) appointed an ad hoc task force to devise and recommend a standard list of tissues to be evaluated histopathologically in repeat-dose toxicity and carcinogenicity studies that are used to support the registration of new pharmaceutical products. The recommended tissue list is intended to be a minimum core list that can be used for all types of repeat-dose toxicity and carcinogenicity studies, regardless of route of administration, species or strain of mammalian laboratory animal, duration, or class of drug to be tested. The resulting recommendations of the task force, presented here, were subsequently reviewed by the STP membership and endorsed by the STP Executive Committee.

The Executive Committee of the Society of Toxicologic Pathology (STP) appointed an ad hoc task force to devise and recommend a standard list of tissues to be evaluated histopathologically in repeat-dose toxicity and carcinogenicity studies that are used to support the registration of new pharmaceutical products. The recommended tissue list is intended to be a minimum core list that can be used for all types of repeat-dose toxicity and carcinogenicity studies, regardless of route of administration, species or strain of mammalian laboratory animal, duration, or class of drug to be tested. The resulting recommendations of the task force, presented here, were subsequently reviewed by the STP membership and endorsed by the STP Executive Committee.

The beagle is a monoestric, nonseasonal breeder with a long estrous cycle. Owing to lengthy stages in individual phases of the estrous cycle, limited group size, and typical group assignment focused on homogenized body weight, dogs in the same stage of the cycle can be inadvertently assigned to one treatment group in toxicity studies potentially leading to erroneous interpretation. This study was conducted to better understand the frequency of the different stages of the cycle and review the associated histological features. Histologic sections of reproductive tissues were reviewed from 102 control dogs from thirty-two GLP studies. The average age of dogs at necropsy was 14.38 months, and the mean terminal body weight was 6.87 kg. Based on histological classification, fifty-five dogs were in anestrus, twenty-eight in diestrus, nine in estrus, five in proestrus, and five were classified as immature. Mean ovarian weights were higher in the estrus stage. This review indicates that more than 80% of the dogs in this study were in the anestrus-diestrus stage, and a small percentage of dogs were immature. Interpretation of drug-induced effects on the morphologic changes in the reproductive tract should be performed with due consideration given to the stage of the cycle and the potential for nonuniform assignment to drug treatment groups.