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Retinoic Acid Antagonizes Testis Development in Mice.

Authors
  • Bowles, Josephine1
  • Feng, Chun-Wei2
  • Ineson, Jessica2
  • Miles, Kim3
  • Spiller, Cassy M4
  • Harley, Vincent R5
  • Sinclair, Andrew H6
  • Koopman, Peter3
  • 1 Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia; School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: [email protected] , (Australia)
  • 2 Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia; School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia. , (Australia)
  • 3 Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia. , (Australia)
  • 4 School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia. , (Australia)
  • 5 Hudson Institute of Medical Research, Clayton, Melbourne, VIC 3168, Australia. , (Australia)
  • 6 Murdoch Children's Research Institute and Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, VIC 3052, Australia. , (Australia)
Type
Published Article
Journal
Cell Reports
Publisher
Elsevier
Publication Date
Jul 31, 2018
Volume
24
Issue
5
Pages
1330–1341
Identifiers
DOI: 10.1016/j.celrep.2018.06.111
PMID: 30067986
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Mammalian sex determination depends on a complex interplay of signals that promote the bipotential fetal gonad to develop as either a testis or an ovary, but the details are incompletely understood. Here, we investigated whether removal of the signaling molecule retinoic acid (RA) by the degradative enzyme CYP26B1 is necessary for proper development of somatic cells of the testes. Gonadal organ culture experiments suggested that RA promotes expression of some ovarian markers and suppresses expression of some testicular markers, acting downstream of Sox9. XY Cyp26b1-null embryos, in which endogenous RA is not degraded, develop mild ovotestes, but more important, steroidogenesis is impaired and the reproductive tract feminized. Experiments involving purified gonadal cells showed that these effects are independent of germ cells and suggest the direct involvement of the orphan nuclear receptor DAX1. Our results reveal that active removal of endogenous RA is required for normal testis development in the mouse. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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