2005 Fiscal Year Final Research Report Summary
Function of erythropoietin and control of its expression in reproductive organs
| Project/Area Number |
14390045
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
広領域
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| Research Institution | The University of Shiga Prefecture |
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Principal Investigator |
SASAKI Ryuzo The Univ.Shiga Pre., Dept.of Life style studies, Professor (60077378)
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| Project Period (FY) |
2002 – 2005
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| Keywords | erythropoietin / reproductive organs / testis / epididymis / Quinolinate / Quinolinate metabolism / sperm |
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| Research Abstract |
It has been believed that stimulation of erythropoiesis is a sole physiological function of erythropoietin (EPO). But we demonstrated that EPO plays an important role in brain ; EPO exerts neuroprotective function in the central nervous system. Other laboratories have supported this finding. Clinical trial of EPO has been successful for brain damage caused by stroke. In addition we have shown that EPO is also produced in the uterus where EPO acts as an angiogenic factor for periodical growth of uterine endometrial layer. EPO production in the uterus is hypoxia-inducible as it is in the kidney and brain. This project is mainly aimed to explore expression of EPO in the male reproductive organs and to find importance of EPO in these organs.
Testis and epididymis from mice were cultured and EPO in the culture supernatant was assayed. Both organs produced EPO but epididymis produced EPO in much larger amount than testis did. Messenger RNA of EPO was also higher in epididymis than that in testis. Sexual maturation (from 3 weeks to 7 weeks) accompanied remarkable increase of EPO mRNA (120-fold increase) in epididymis. It is possible that EPO is involved in the process by which sperms gain fertility capability, because this event occurs in the epididymis to where sperms are transported from testis.
In the meantime, it was shown that quinolinate (QA), a metabolic intermediate in the metabolic pathway from tryptophan to NAD, inhibits EPO production. When we can accumulate QA and thereby EPO production depressed, we may be able to find a role EPO in the reproductive organs. We have decided to destroy quinolinate phosphoribosyltransferase gene that is responsible for QA metabolism but this project has not yet completed. Phthalate was found to accumulate QA and therefore we may be able to elucidate a role of EPO in the reproductive organs.
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