Wnt signalling in testicular descent: A candidate mechanism for cryptorchidism in Robinow syndrome

George N. Harisis, Nan Chen, Pamela J. Farmer, Daniela Bodemer, Ruili Li, Magdy Sourial, Bridget R. Southwell, Adam Balic, John M. Hutson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background/Aims: Robinow syndrome is caused by mutations in Wnt-5a or its receptor Ror2 and can lead to cryptorchidism, though the mechanisms are unclear. Wnt-5a knock-out mice fail to undergo gubernacular swelling, similar to insulin-like hormone 3 (INSl-3) knock-out mice. We aimed to characterise Wnt-5a and Ror2 expression in rat gubernacula to better understand how Wnt-5a signalling affects testicular descent.

Methods: Sprague-Dawley rats (n=27) were collected with ethics approval (A644) at embryonic days (E) 15, 17, 19 and postnatal day (D) 2. Control and antiandrogen-treated groups were processed for immunohistochemistry for Wnt-5a, Ror2 and beta-catenin. Sagittal sections were examined using confocal microscopy.

Results: Wnt-5a and Ror2 were strongly expressed in the gubernacular bulb at E17 controls, their levels declining at E19 and almost absent by D2. Wnt-5a significantly co-localised with the important transcription factor beta-catenin at E17. There was no obvious difference in staining with androgen blockade.

Conclusion: Wnt-5a, through Ror2 and beta-catenin may play a vital role in regulating the gubernacular swelling reaction downstream of INSL-3. Human mutations in Wnt-5a or Ror2 could prevent early gubernacular growth, as suggested by undescended testes in 70% of patients with Robinow Syndrome. (C) 2013 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)1573-1577
Number of pages5
JournalJournal of Pediatric Surgery
Volume48
Issue number7
DOIs
Publication statusPublished - Jul 2013
EventNational Conference and Exhibition of the Surgical-Section of the American-Academy-of-Pediatrics - Boston, Morocco
Duration: 15 Oct 201118 Oct 2011

Keywords

  • Testicular descent
  • Cryptorchidism
  • Robinow syndrome
  • Wnt-5a
  • Gubernaculum
  • PLANAR CELL POLARITY
  • AUTOSOMAL-DOMINANT
  • ROR2
  • MICE
  • DISRUPTION
  • INSL3

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