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J. Biol. Chem., Vol. 278, Issue 46, 45843-45847, November 14, 2003

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Uncoupling Protein 2, but Not Uncoupling Protein 1, Is Expressed in the Female Mouse Reproductive Tract^*

Sophie Rousset, Marie-Clotilde Alves-Guerra¶, Salma Ouadghiri-Bencherif||, Leslie P. Kozak**, Bruno Miroux, Denis Richard||, Frédéric Bouillaud, Daniel Ricquier, and Anne-Marie Cassard-Doulcier

From the CNRS, Unité Propre de Recherche 9078, Faculté de Médecine Necker-Enfants malades, 156 rue de Vaugirard, 75730 Paris Cedex 15, France, the ^||Département d'anatomie et de physiologie, Faculté de médecine, Université Laval, Québec G1K 7P4, Canada, and the ^**Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808

Uncoupling proteins (UCPs) are transporters of the inner mitochondrial membrane. Whereas UCP1 is uniquely present in brown adipose tissue where it uncouples respiration from ATP synthesis and activates respiration and heat production, UCP2 is present in numerous tissues, and its exact function remains to be clarified. Two sets of data provided the rationale for this study: (i) the intriguing report that UCP1 is present in uterus of mice (Nibbelink, M., Moulin, K., Arnaud, E., Duval, C., Penicaud, L., and Casteilla, L. (2001) J. Biol. Chem. 276, 47291-47295); and (ii) an observation that Ucp2(-/-) female mice (homozygous matings) have smaller litters compared with Ucp2(+/+) animals (S. Rousset and A.-M. Cassard-Doulcier, unpublished observations). These data prompted us to examine the expression of UCP1 and UCP2 in the reproductive tract of female mice. Using wild type, Ucp1(-/-) mice, and Ucp2(-/-) mice, we were unable to detect UCP1 in uterus of mice with appropriate antibodies, and we conclude that the signal assigned to UCP1 by others was neither UCP1 nor UCP2. Using a polyclonal antibody against UCP2 and tissues from Ucp2(-/-) mice as controls, UCP2 was detected in ovary, oviduct, and uterus. Expression of Ucp2 mRNA was also observed in ovary and uterus using in situ hybridization analysis. Bone marrow transplantation experiments revealed that the UCP2 signal of the ovary was restricted to ovarian cells. UCP2 level in ovary decreased during follicular growth and increased during the pre-ovulatory period, during which aspects of an inflammatory process are known to exist. Because UCP2 down-regulates reactive oxygen species, a role in the regulation of inflammatory events linked to the preparation of ovulation is suggested.

Received for publication, July 1, 2003 , and in revised form, August 26, 2003.

^* This work was supported in part by CNRS, INSERM, the Association pour la Recherche contre le Cancer (ARC), and the Institut de Recherche Servier. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by a grant from the Ministère de la Recherche.

^¶ Supported by a grant from Glaxo-Smith-Kline.

To whom correspondence should be addressed. Tel.: 33-1-40-61-56-97; E-mail: cassard-doulcier{at}necker.fr.

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