Epididymis is a novel site of erythropoietin production in mouse reproductive organs

Graduate School of Biostudies, Kyoto University, Kioto, Kyōto, Japan
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 09/2002; 296(1):145-51. DOI: 10.1016/S0006-291X(02)00832-X
Source: PubMed


The epididymis consists of the interstitial tissue and the ductus epididymidis, an extremely tortuous duct, in which spermatozoa exported from the testis gain motility and fertilizing capacity. We found that the cultured mouse epididymis produces erythropoietin (Epo). The content of Epo mRNA in the epididymis from the adult mouse (8-week-old) amounts to 40% of that in the kidney. The epididymal Epo mRNA dramatically increased upon growth; its level increased 120-fold from the age of 3 weeks to 7 weeks when they complete sexual maturation, while the increase in the total RNA was 3-fold. Hypoxia induced a 5-fold increase in the epididymal Epo mRNA transiently, which is much lower than the induction in the kidney (28-fold). In situ hybridization technique elucidated that the site of Epo production was located in the interstitial space between ductus epididymidis. The epididymal Epo may have an unidentified function in the male reproductive organ.

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    • "In situ hybridization 4 h hypoxia (7% O 2 ) was applied before the sacrifice of mice [22]. "
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    ABSTRACT: Erythropoietin production has been reported to occur in the peritubular interstitial fibroblasts in the kidney. Since the erythropoietin production in the nephron is controversial, we reevaluated the erythropoietin production in the kidney. We examined mRNA expressions of erythropoietin and HIF PHD2 using high-sensitive in situ hybridization system (ISH) and protein expression of HIF PHD2 using immunohistochemistry in the kidney. We further investigated the mechanism of erythropoietin production by hypoxia in vitro using human liver hepatocell (HepG2) and rat intercalated cell line (IN-IC cells). ISH in mice showed mRNA expression of erythropoietin in proximal convoluted tubules (PCTs), distal convoluted tubules (DCTs) and cortical collecting ducts (CCDs) but not in the peritubular cells under normal conditions. Hypoxia induced mRNA expression of erythropoietin largely in peritubular cells and slightly in PCTs, DCTs, and CCDs. Double staining with AQP3 or AE1 indicated that erythropoietin mRNA expresses mainly in β-intercalated or non α/non β-intercalated cells of the collecting ducts. Immunohistochemistry in rat showed the expression of HIF PHD2 in the collecting ducts and peritubular cells and its increase by anemia in peritubular cells. In IN-IC cells, hypoxia increased mRNA expression of erythropoietin, erythropoietin concentration in the medium and protein expression of HIF PHD2. These data suggest that erythropoietin is produced by the cortical nephrons mainly in the intercalated cells, but not in the peritubular cells, in normal hematopoietic condition and by mainly peritubular cells in hypoxia, suggesting the different regulation mechanism between the nephrons and peritubular cells.
    Biochemical and Biophysical Research Communications 06/2014; 449(2). DOI:10.1016/j.bbrc.2014.05.014 · 2.30 Impact Factor
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    • "Thus, this hormone is actually used to treat anaemia in patients with cancer, or in patients with renal disease and anaemia based on their deficient Epo production. However, although kidney and liver are the two major sources of Epo synthesis, Epo mRNA expression has also been found in some other tissues, including the brain (neurons and glial cells), lung, heart, bone marrow, spleen, hair follicles, reproductive tract, and osteoblasts [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16]. Accordingly , Epo receptor (EpoR) has been detected in neurons, astrocytes, microglia, immune cells, cancer cell lines, endothelial cells, bone marrow stromal cells, as well as in cells of heart, reproductive system, gastrointestinal tract, kidney, pancreas and skeletal muscle [17] [18] [19] [20] [21] [22] [23] [24] [25] [26], thus providing evidence for pleitropic action [27] [28]. "
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    ABSTRACT: Erythropoietin (Epo) has been thought to act exclusively on erythroid progenitor cells. The identification of Epo receptor (EpoR) in non-haematopoietic cells and tissues including neurons, astrocytes, microglia, immune cells, cancer cell lines, endothelial cells, bone marrow stromal cells, as well as cells of myocardium, reproductive system, gastrointestinal tract, kidney, pancreas and skeletal muscle indicates that Epo has pleiotropic actions. Epo shows signals through protein kinases, anti-apoptotic proteins and transcription factors. In light of interest of administering recombinant human erythropoietin (rhEpo) and its analogues for limiting infarct size and left ventricular (LV) remodelling after acute myocardial infarction (AMI) in humans, the foremost studies utilising rhEpo are reviewed. The putative mechanisms involved in Epo-induced cardioprotection are related to the antiapoptotic, anti-inflammatory and angiogenic effects of Epo. Thus, cardioprotective potentials of rhEpo are reviewed in this article by focusing on clinical applicability. An overview of non-haematopoietic Epo analogues, which are a reliable alternative to the classic EpoR agonists and may prevent undesired side effects, is also provided.
    International journal of cardiology 12/2013; 171(2). DOI:10.1016/j.ijcard.2013.12.011 · 4.04 Impact Factor
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    • "Interestingly, the temporal pattern of Epo secretion by the epididymis resembles that of the kidney: there is an initial peak, followed by a phase of downregulation, which contrasts with the response of other organs that exhibit a more sustained secretory response (Kobayashi et al, 2002). Accordingly, it has been speculated that the epididymis may be a source of circulating Epo (Kobayashi et al, 2002). This notion has recently been supported by the demonstration of the presence of hypoxia-inducible factor-1 in the rat epididymis (Palladino et al, 2004), which is a transcription factor that activates several genes involved in oxygen homeostasis, including Epo. "

    Journal of Andrology 02/2006; 27(3):348-57. DOI:10.2164/jandrol.05182 · 2.47 Impact Factor
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