Original articleWnt signalling in testicular descent: A candidate mechanism for cryptorchidism in Robinow syndrome☆,☆☆
Section snippets
Methods
All experiments were approved by the institutional animal ethics committee (A644). Time-mated Sprague–Dawley dams were randomly allocated into either a control group or a group administered the anti-androgen flutamide according to a previously described method [11]. Pregnant dams were kept in the institute's Animal Research Laboratory and housed in standard shoe-box cages in a temperature-controlled environment with 12-h light/dark cycles. Animals were fed commercial rat chow and had access to
Wnt-5a was expressed in the E17 rat gubernaculum (n = 10)
At E17, Wnt-5a was strongly expressed in the tip of the male rat gubernaculum and around cells of the developing cremaster muscle. Expression appeared reduced in both areas by E19 (n = 10) and was absent by D2 (n = 9), coinciding with the beginning of inguino-scrotal migration (Fig. 1A-C). There was no qualitative difference in staining between control and antiandrogen-treated rats at E19 ( and D2 (n = 7) (not shown).
The Wnt-5a receptor Ror2 was maximally expressed in the E17 gubernaculum (n = 10 gubernacula)
Ror2, the non-canonical receptor for Wnt-5a, was strongly expressed in the
Discussion
We report for the first time, immunolocalisation of Wnt-5a and its receptor Ror2 within the rat gubernaculum. Wnt-5a expression was strongest in the gubernacular bulb and cremaster muscle at E17 during the critical period of active growth and swelling known to be controlled by INSL-3, and required to facilitate transabdominal testicular descent [19], [20]. Levels of Wnt-5a within the bulb rapidly decreased following gubernacular eversion and migration towards the scrotum (D2). Similarly,
Limitations
Although fluorescence immunohistochemistry is useful for visualisation of particular antigens, quantification of antigen expression is sometimes difficult to ascertain. It was not possible to conduct rigorous statistical analyses which could confirm the observed changes of these factors over time. However, it was possible to replicate the qualitative immunohistochemical findings in many specimens. Alternate techniques such as real-time PCR would be more suitable for the purposes of
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2023, Journal of Asia-Pacific EntomologyEnvironmental toxicants and cell polarity in the testis
2018, Reproductive ToxicologyCitation Excerpt :It is envisioned that more functional studies are needed to unravel the role of PCP proteins in environmental toxicant-induced testis injury. In this context, it is of interest to note that transgenic deletion of Wnt signaling pathways in mice, such as Vangl2, Sfrp1/Sfrp2, Ctnnb, or Wnt5a, led to cryptorchidism and/or gubernacular maldevelopment [66–71]. However, if mutations of any of these genes including Vangl2 would cause human cryptorchidism remains to be established.
The variations in the AXIN1 gene and susceptibility to cryptorchidism
2015, Journal of Pediatric UrologyCitation Excerpt :The importance of Wnt signaling in mouse embryonic and postnatal development and in diseases has been reported by several authors [5,12,20–22]. Activation of Wnt signaling has been revealed as the underlying etiology of some cryptorchidisms [9]. AXIN1, the wild-type AXIN gene, a negative regulator of this pathway, has been suggested to play an important role during embryogenesis.
The C-Cbl ubiquitin ligase regulates nuclear β-catenin and angiogenesis by its tyrosine phosphorylation mediated through the Wnt signaling pathway
2015, Journal of Biological ChemistryCitation Excerpt :The germ line c-Cbl mutations have developmental and functional consequences (28). Hyperactive Wnt signaling has been implicated in several of those conditions (29, 30), which now can be linked through the present data. Overall, the c-Cbl-Wnt-β-catenin relationship has implications both in angiogenesis and tumorigenesis.
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2018, Frontiers in Endocrinology
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Supported in part by the National Health and Medical Research Council (Australia), Grant no. ID60736.
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Presented at the 2011 American Academy of Pediatrics National Conference and Exhibition, Boston, USA.