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Unilateral Cryptorchidism in Mice Mutant for Ptgds

Authors

  • Pascal Philibert,

    1. Département d'Hormonologie, Hôpital Lapeyronie, CHU de Montpellier et Université Montpellier 1, France
    2. Groupe Développement et Pathologie de la Gonade, Institut de Génétique Humaine, CNRS UPR 1142, Montpellier, France
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  • Brigitte Boizet-Bonhoure,

    1. Département d'Hormonologie, Hôpital Lapeyronie, CHU de Montpellier et Université Montpellier 1, France
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    • These two authors have contributed equally to this work.

  • Anu Bashamboo,

    1. Département d'Hormonologie, Hôpital Lapeyronie, CHU de Montpellier et Université Montpellier 1, France
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    • These two authors have contributed equally to this work.

  • Françoise Paris,

    1. Département d'Hormonologie, Hôpital Lapeyronie, CHU de Montpellier et Université Montpellier 1, France
    2. Unité d'Endocrinologie et Gynécologie Pédiatrique, Hôpital A. de Villeneuve, CHU de Montpellier et Université Montpellier 1, France
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  • Kosuke Aritake,

    1. Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka, Japan
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  • Yoshihiro Urade,

    1. Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka, Japan
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  • Juliane Leger,

    1. Service d'Endocrinologie Pédiatrique, Hôpital Robert Debré, AP-HP, Paris, France
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  • Charles Sultan,

    1. Département d'Hormonologie, Hôpital Lapeyronie, CHU de Montpellier et Université Montpellier 1, France
    2. Groupe Développement et Pathologie de la Gonade, Institut de Génétique Humaine, CNRS UPR 1142, Montpellier, France
    3. Unité d'Endocrinologie et Gynécologie Pédiatrique, Hôpital A. de Villeneuve, CHU de Montpellier et Université Montpellier 1, France
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  • Francis Poulat

    Corresponding author
    1. Groupe Développement et Pathologie de la Gonade, Institut de Génétique Humaine, CNRS UPR 1142, Montpellier, France
    • Département d'Hormonologie, Hôpital Lapeyronie, CHU de Montpellier et Université Montpellier 1, France
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  • Communicated by Ravi Savarirayan

  • Contract grant sponsor: INSERM: Programme National de Recherche en Reproduction-Endocrinologie (PNRRE 2007 n°0703).

Correspondence to: Francis Poulat, Développement et Pathologie de la Gonade, Institut de Génétique Humaine, CNRS UPR 1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France. E-mail: francis.poulat@igh.cnrs.fr

ABSTRACT

The pathophysiology of cryptorchidism, abnormal testicular descent, remains poorly understood. In this study, we show that both heterozygous and homozygous mice deficient for lipocalin-type prostaglandin D2 (PGD2) synthase (Ptgds) presented unilateral cryptorchidism affecting the second phase of testicular descent in 16% and 24% of cases, respectively. The adult cryptorchid testes show an increase in spermatogonia apoptosis along with a global decrease in the tubule size parameters, whereas the gubernaculum of newborn mutants present some histological abnormalities. Disruption of the inguinoscrotal phase did not present impairment of the androgen pathway but rather a decrease in Rxfp2 mRNA expression in the gubernaculum. These observations led us to investigate the role of the PGD2 signaling pathway in human testicular migration through PTGDS sequencing of DNA from 29 children with cryptorchidism. However, none of the investigated cases presented mutations in the PTGDS gene. Nevertheless, our results identify the PTGDS enzyme as a novel component in the cryptorchidism puzzle.

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