Nuclear receptor signaling plays an important role in energy metabolism. In this study we demonstrate that the nuclear receptor corepressor RIP140 is a key regulator of metabolism in skeletal muscle. RIP140 is expressed in a fiber type-specific manner, and manipulation of its levels in null, heterozygous, and transgenic mice demonstrate that low levels promote while increased expression suppresses the formation of oxidative fibers. Expression profiling reveals global changes in the expression of genes implicated in both myofiber phenotype and metabolic functions. Genes involved in fatty-acid oxidation, oxidative phosphorylation, and mitochondrial biogenesis are upregulated in the absence of RIP140. Analysis of cultured myofibers demonstrates that the changes in expression are intrinsic to muscle cells and that nuclear receptor-regulated genes are direct targets for repression by RIP140. Therefore RIP140 is an important signaling factor in the regulation of skeletal muscle function and physiology.
This study provides a quantitative comparison between surface and ultrastructural features of motile spermatozoa in asthenozoospermic and fertile men. The study group consisted of 10 individuals with persistent asthenozoospermia and the controls were 10 fertile donors to a sperm bank. Scanning electron microscopy and image analysis were used to objectively measure sperm mid-piece and tail dimensions. Sperm mid-piece length was significantly shorter (P < 0.01) in asthenozoospermic subjects compared with the controls, with mid-piece width and tail length being comparable. Mid-piece ultrastructure was then examined with the transmission electron microscope and the number of mitochondrial gyres and their configuration recorded. At the ultrastructural level the asthenozoospermic subjects demonstrated significantly fewer mitochondrial gyres (P < 0.001) than their fertile counterparts. Energy for sperm movement is provided by mitochondria and a deficit in these organelles in the sub-fertile cohort provides an explanation for poor sperm function in these subjects.
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