ABSTRACT
BACKGROUND: Adiponectin (Adipoq), a protein secreted by adipocytes in inverse proportion to the adipose mass present, modulates energy homeostasis and increases insulin sensitivity. Tissue Adipoq signaling decreases in settings of maternal diabetes, polycystic ovary syndrome (PCOS) and endometriosis, conditions which are associated with reproductive difficulty. Our objective was to define the expression and hormonal regulation of Adipoq and its receptors in the mouse preimplantation embryo and uterus. METHODS AND RESULTS: By real-time quantitative PCR, mRNA transcripts for Adipoq, AdipoR1, AdipoR2, Ppara, Ppard, FATP1 (SLC27A1) and acyl CoA oxidase (Acox1) were identified in mouse 2-cell and 8-cell embryos, while blastocyst stage embryos and trophoblast stem (TS) cells expressed mRNA for all genes except Adipoq. Protein expression of Adipoq, AdipoR1, AdipoR2, the insulin sensitive transporters GLUT8 (Slc2A8), GLUT12 (Slc2A12) and p-PRKAA1 was identified by immunofluorescence staining in all stages of preimplantation embryos including the blastocyst. In situ hybridization demonstrated the presence of Adipoq, AdipoR1 and AdipoR2 mRNA in the mouse decidual cells of the implantation site and in artificially decidualized cells, and the expression of these proteins was confirmed by western blotting. Flow cytometry confirmed cell surface expression of AdipoR1 and AdipoR2 in TS cells and decidual cells. CONCLUSIONS: These results suggest for the first time that Adipoq signaling may play an important role in preimplantation embryo development and uterine receptivity by autocrine and paracrine methods in the mouse. Implantation failures and pregnancy loss, specifically those experienced in women with maternal metabolic conditions such as diabetes, obesity and PCOS, may be the result of aberrant Adipoq and AdipoR1 and AdipoR2 expression and suboptimal decidualization in the uterus.
Subject(s)
Adiponectin/metabolism , Blastocyst/metabolism , Decidua/metabolism , Receptors, Adiponectin/metabolism , Adiponectin/genetics , Adiponectin/physiology , Animals , Blotting, Western , Embryo Implantation , Embryonic Development , Female , Flow Cytometry , Gene Expression Regulation, Developmental , Glucose Transport Proteins, Facilitative/metabolism , In Situ Hybridization , Mice , Polymerase Chain Reaction , RNA, Messenger/metabolism , Receptors, Adiponectin/genetics , Receptors, Adiponectin/physiology , Signal TransductionABSTRACT
Meiotic dysfunction increasingly afflicts women as they age, resulting in infertility, miscarriage and handicapped offspring. How aging disrupts meiotic function in women remains unclear, but as women increasingly delay childbearing, this issue becomes urgent. Telomeres, which mediate aging in mitotic cells, may also mediate aging during meiosis. Telomeres shorten during DNA replication. In mammals, oocytes remain quiescent, but their precursors replicated during fetal oogenesis. Moreover, eggs ovulated from older women entered meiosis later during fetal oogenesis than eggs ovulated when younger, and therefore underwent more replications. Telomeres also shorten from reactive oxygen, which triggers a DNA repair response, so the prolonged interval between fetal oogenesis and ovulation in some women would further shorten telomeres. Mice normally do not exhibit age-related meiotic dysfunction (interestingly, their telomeres are manyfold longer than telomeres in women), but genetic or pharmacologic shortening of mouse telomeres recapitulates the reproductive aging phenotype of women. This has led to a telomere theory of age-related meiotic dysfunction in women, and underlined the importance to human health of a mechanistic understanding of telomeres and meiosis.
Subject(s)
Cellular Senescence/genetics , Meiosis/physiology , Nondisjunction, Genetic/genetics , Reproduction/genetics , Telomere/physiology , Animals , Cellular Senescence/physiology , Female , Humans , Mice , Reproduction/physiology , Spindle Apparatus/physiology , Telomere/geneticsABSTRACT
Lymphatic filariasis is caused by infection with the filarial nematodes Brugia malayi, Brugia timori, Wuchereria bancrofti and Onchocerca volvulus which collectively infect about 200 million persons throughout the world. Protein sequence homology analysis of a major nematode antigen suggested that it was a class II aminoacyl-tRNA synthetase. The overproduction, purification and verification that the major B. malayi antigen is an asparaginyl-tRNA synthetase is described.
Subject(s)
Amino Acyl-tRNA Synthetases/immunology , Antigens, Helminth/immunology , Aspartate-tRNA Ligase , Brugia malayi/immunology , Immunodominant Epitopes/immunology , RNA, Transfer, Amino Acyl , RNA, Transfer, Asn , Amino Acid Sequence , Amino Acyl-tRNA Synthetases/genetics , Animals , Antigens, Helminth/genetics , Base Sequence , DNA Primers , Immunodominant Epitopes/genetics , Molecular Sequence Data , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunologyABSTRACT
Five children with Leigh's disease and progressive neurological symptoms were compared with 14 control children. In all patients, MRI showed bilateral lesions of the putamina and caudate heads. Serum lactate was normal for four of the children, and CSF lactate slightly elevated for three. Volume-selective proton MR spectroscopy (1H-MRS) of the basal ganglia in the Leigh patients revealed elevated lactate, giving further evidence for a defect of energy metabolism in the brain. 1H-MRS is an important tool for non-invasive brain tissue analysis in Leigh's disease, particularly in the absence of peripheral lactate elevation.
Subject(s)
Brain Diseases/diagnosis , Brain Diseases/metabolism , Brain/diagnostic imaging , Developmental Disabilities/diagnosis , Leigh Disease/diagnosis , Leigh Disease/metabolism , Pyruvate Dehydrogenase Complex/analysis , Acidosis, Lactic/cerebrospinal fluid , Basal Ganglia/ultrastructure , Brain/enzymology , Brain Diseases/complications , Child, Preschool , Developmental Disabilities/etiology , Diagnosis, Differential , Female , Humans , Infant , Lactates/cerebrospinal fluid , Magnetic Resonance Spectroscopy , Male , Mitochondria/enzymology , Radionuclide ImagingABSTRACT
A case of delayed revascularisation surgery three days after a traumatic renal artery thrombosis is presented. Criteria for a successful operation, with saving of the involved organ, are: normal kidney size, intact glomeruli and visualization of the kidney by contrast-medium.
