ABSTRACT
In humans, all but 1% of monosomy 45.X embryos die in utero and those who reach term suffer from congenital abnormalities and infertility termed Turner's syndrome (TS). By contrast, XO female mice on various genetic backgrounds show much milder physical defects and normal fertility, diminishing their value as an animal model for studying the infertility of TS patients. In this article, we report that XO mice on the C57BL/6J (B6) genetic background showed early oocyte loss, infertility or subfertility and high embryonic lethality, suggesting that the effect of monosomy X in the female germline may be shared between mice and humans. First, we generated XO mice on either a mixed N2(C3H.B6) or B6 genetic background and compared the number of oocytes in neonatal ovaries; N2.XO females retained 45% of the number of oocytes in N2.XX females, whereas B6.XO females retained only 15% of that in B6.XX females. Second, while N2.XO females were as fertile as N2.XX females, both the frequency of delivery and the total number of pups delivered by B6.XO females were significantly lower than those by B6.XX females. Third, after mating with B6 males, both N2.XO and B6.XO females rarely produced XO pups carrying paternal X chromosomes, although a larger percentage of embryos was found to be XO before implantation. Furthermore, B6.XO females delivered 20% XO pups among female progeny after mating with C3H males. We conclude that the impact of monosomy X on female mouse fertility depends on the genetic background.
Subject(s)
Genetic Background , Primary Ovarian Insufficiency/genetics , Turner Syndrome/genetics , Animals , Female , Infertility, Female/genetics , Infertility, Female/pathology , Male , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Monosomy/genetics , Monosomy/pathology , Pedigree , Primary Ovarian Insufficiency/etiology , Primary Ovarian Insufficiency/pathology , Turner Syndrome/complications , X Chromosome/geneticsABSTRACT
OBJECTIVE: 12/15-Lipoxygenase (12/15-LOX) catalyzes the generation of various anti-inflammatory lipid mediators, and has been implicated in several inflammatory and degenerative diseases. However, there is currently no evidence that 12/15-LOX has a role in osteoarthritis (OA). The aim of this study was to investigate the role of 12/15-LOX in the pathogenesis of OA. METHODS: The development of aging-associated and destabilization of the medial meniscus (DMM)-induced OA were compared in 12/15-LOX-deficient (12/15-LOX-/-) and wild-type (WT) mice. The extent of cartilage damage was evaluated by histology. The expression of OA markers was evaluated by immunohistochemistry and RT-PCR. Cartilage explants were stimulated with IL-1α in the absence or presence of the 12/15-LOX metabolites, 15-hydroxyeicosatetraenoic acids (15-HETE), 13-hydroxyoctadecadienoic acid (13-HODE) or lipoxin A4 (LXA4), and the levels of matrix metalloproteinases-13 (MMP-13), Nitric oxide (NO) and prostaglandin E2 (PGE2) were determined. The effect of LXA4 on the progression of OA was evaluated in wild type (WT) mice. RESULTS: The expression of 12/15-LOX in cartilage increased during the progression of DMM-induced OA and with aging in WT mice. Cartilage degeneration was more severe in 12/15-LOX-/- mice compared to WT mice in both models of OA, and this was associated with increased expression of MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs, aggrecanases (ADAMTS5), inducible NO synthases (iNOS), and mPGES-1. Treatment of cartilage explants with 12/15-LOX metabolites, suppressed IL-1α-induced production of MMP-13, NO and PGE2, with LXA4 being the most potent. Intra-peritoneal injection of LXA4 reduced the severity of DMM-induced cartilage degradation. CONCLUSIONS: These data suggest an important role of 12/15-LOX in the pathogenesis of OA. They also suggest that activation of this pathway may provide a novel strategy for prevention and treatment of OA.
Subject(s)
Arachidonate 12-Lipoxygenase/physiology , Arachidonate 15-Lipoxygenase/physiology , Arthritis, Experimental/enzymology , Osteoarthritis/enzymology , Aging/metabolism , Aging/pathology , Animals , Arachidonate 12-Lipoxygenase/deficiency , Arachidonate 12-Lipoxygenase/genetics , Arachidonate 15-Lipoxygenase/deficiency , Arachidonate 15-Lipoxygenase/genetics , Arthritis, Experimental/etiology , Arthritis, Experimental/prevention & control , Cartilage, Articular/metabolism , Disease Progression , Inflammation Mediators/metabolism , Joint Instability/complications , Lipoxins/therapeutic use , Male , Mice, Knockout , Osteoarthritis/etiology , Osteoarthritis/prevention & control , Tibial Meniscus Injuries/complications , Tissue Culture Techniques , Up-RegulationABSTRACT
The authors report 15 cases of gangrene of the perineum and genital organs: 10 patients with urological lesions (urethral stricture: 6 cases, benign prostatic hypertrophy: 3 cases, bladder stones: 1 case) and 5 patients with Fournier's disease. The unexpected recrudescence of this disease, its persistent severity, the limits of our understanding of the pathogenesis and the therapeutic problems involved, led the authors to analyse this series of cases which, despite an apparent diversity of aetiologies, retained common anatomical, bacteriological and therapeutic features. They stress the importance of emergency surgery, appropriate antibiotics and postoperative intensive care. The mortality remains high (5 patients in this series died).
Subject(s)
Genital Diseases, Male/diagnosis , Genital Diseases, Male/therapy , Perineum/pathology , Adolescent , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Combined Modality Therapy , Debridement , Gangrene/diagnosis , Gangrene/drug therapy , Gangrene/pathology , Gangrene/surgery , Gangrene/therapy , Genital Diseases, Male/drug therapy , Genital Diseases, Male/pathology , Genital Diseases, Male/surgery , Humans , Male , Middle AgedABSTRACT
We report a case of mucin-producing adenocarcinoma of the urachus. Preoperative diagnosis was established by computerized axial tomography. An en bloc resection was performed, including the urachus with supravesical mass and bladder dome.
