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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Deficient tryptophan catabolism along the kynurenine pathway reveals that the epididymis is in a unique tolerogenic state
Journal of Biological Chemistry, Volume 286, No. 10, Year 2011
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Description
Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting enzyme of tryptophan catabolism through the kynurenine pathway. Intriguingly, IDO is constitutively and highly expressed in the mammalian epididymis in contrast to most other tissues where IDO is induced by proinflammatory cytokines, such as interferons. To gain insight into the role of IDO in the physiology of the mammalian epididymis, we studied both wild type and Ido1-/--deficient mice. In the caput epididymis of. Ido1-/- animals, the lack of IDO activity was not compensated by other tryptophan-catabolizing enzymes and led to the loss of kynurenine production. The absence of IDO generated an inflammatory state in the caput epididymis as revealed by an increased accumulation of various inflammation markers. The absence of IDO also increased the tryptophan content of the caput epididymis and generated a parallel increase in caput epididymal protein content as a consequence of deficient proteasomal activity. Surprisingly, the lack of IDO expression had no noticeable impact on overall male fertility but did induce highly significant increases in both the number and the percentage of abnormal spermatozoa. These changes coincided with a significant decrease in white blood cell count in epididymal fluid compared with wild type mice. These data provide support for IDO playing a hitherto unsuspected role in sperm quality control in the epididymis involving the ubiquitination of defective spermatozoa and their subsequent removal. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
Authors & Co-Authors
Jrad-Lamine, Aicha
France, Clermont-ferrand
Université Clermont Auvergne
Henry-Berger, Joelle
France, Clermont-ferrand
Université Clermont Auvergne
Gourbeyre, Pascal
France, Nantes
Biopolymères, Interactions Assemblages Bia
Damon-Soubeyrand, Christelle
France, Clermont-ferrand
Université Clermont Auvergne
Lenoir, Alain
France, Clermont-ferrand
Université Clermont Auvergne
Combaret, Lydie
France, Saint-genes-champanelle
Unité de Nutrition Humaine Unh
Saez, Fabrice
France, Clermont-ferrand
Université Clermont Auvergne
Kocer, Ayhan
France, Clermont-ferrand
Université Clermont Auvergne
Tone, Shigenobu
Japan, Kurashiki
Kawasaki Medical School
Fuchs, Dietmar N.
Austria, Innsbruck
Medizinische Universitat Innsbruck
Zhu, Wentao
Germany, Regensburg
Universität Regensburg
Oefner, Peter J.
Germany, Regensburg
Universität Regensburg
Munn, David H.
United States, Augusta
Medical College of Georgia
Mellor, Andrew L.
United States, Augusta
Medical College of Georgia
Gharbi, Najoua
Tunisia, Tunis
Université de Tunis el Manar, Faculté Des Sciences de Tunis
Cadet, Rémi
France, Clermont-ferrand
Université Clermont Auvergne
Aitken, Robert J.
Australia, Callaghan
School of Environmental and Life Sciences
Drevet, Joël R.
France, Clermont-ferrand
Université Clermont Auvergne
Statistics
Citations: 46
Authors: 18
Affiliations: 9
Identifiers
Doi:
10.1074/jbc.M110.172114
ISSN:
00219258
e-ISSN:
1083351X
Research Areas
Sexual And Reproductive Health
Participants Gender
Male