No abstract

No abstract

No abstract

Lack of animal models with human-like size and pathology hampers translational research in atherosclerosis. Mouse models are missing central features of human atherosclerosis and are too small for intravascular procedures and imaging. Modeling the disease in minipigs may overcome these limitations, but it has proven difficult to induce rapid atherosclerosis in normal pigs by high-fat feeding alone, and genetically modified models similar to those created in mice are not available. D374Y gain-of-function mutations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene cause severe autosomal dominant hypercholesterolemia and accelerates atherosclerosis in humans. Using Sleeping Beauty DNA transposition and cloning by somatic cell nuclear transfer, we created Yucatan minipigs with liver-specific expression of human D374Y-PCSK9. D374Y-PCSK9 transgenic pigs displayed reduced hepatic low-density lipoprotein (LDL) receptor levels, impaired LDL clearance, severe hypercholesterolemia, and spontaneous development of progressive atherosclerotic lesions that could be visualized by noninvasive imaging. This model should prove useful for several types of translational research in atherosclerosis.

Summary. Cows and heifers were induced to superovulate by treatment with PMSG or FSH. The ultrastructural features of the oocytes were related to the time of the LH peak and the progesterone/oestradiol-17\g=b\ ratios in the follicular fluid.At 0\p=n-\2h after the LH peak the perivitelline space developed; at 9\p=n-\12h there was disconnection of the junctions between cumulus cell projections and oolemma, and the concomitant breakdown of the oocyte nucleus; at \m=~\15 h there were spatial rearrangements in the ooplasm of (a) mitochondrial clusters from a peripheral to an even distribution and (b) vesicles from an even distribution to a more central location; at \m=~\19 h there was abstriction of the first polar body with dislocation of mitochondrial clusters and vesicles towards the site of polar body formation; at 21\p=n-\22h there was migration of cortical granules to solitary positions along the oolemma and decrease in the sizes of Golgi complexes and, on some occasions, the smooth endoplasmic reticulum. These ultrastructural changes were accompanied by an increase in progesterone/oestradiol ratios in the follicular fluids.It is concluded that preovulatory oocyte maturation in gonadotrophin-stimulated cattle comprises nuclear as well as cytoplasmic changes accompanied by steroidogenic changes in the follicle, each of which are closely related to the time of the LH peak.However, some variation existed between animals, between follicular and oocyte maturation and even within oocytes between nuclear and cytoplasmic maturation.