BDNF is upregulated by androgen in the inguinal fat pad of immature mice and may regulate inguinoscrotal testicular descent

Abstract

Background: Androgens control rodent inguinoscrotal testicular descent during a "programming window" (E12-17). It is proposed that androgen masculinises the genitofemoral nerve, but the mechanism remains unknown. We investigate androgen receptor (AR)-containing target organs: inguinal fat pad (IFP) and mammary bud (MB), supplied by the genitofemoral nerve, hypothesizing that neurotrophic factors may retrogradely masculinise the GFN.

Methods: The IFP, MB and bulbocavernosus (BC) muscle were collected at E12.5/E17.5 from androgen receptor knockout (ARKO) mice and wild-type (WT) littermates. Immunofluorescence and gene expression (RT-qPCR; n = 8/group) for Bdnf, active (TrkB) and inactive (truncated TrkB) receptors, Cntf and Cntf receptor were performed.

Results: In the IFP at E12.5, ARKO TrkB mRNA expression was significantly downregulated compared to WT males (p < 0.0026). By E17.5, there was increased Bdnf expression (p < 0.0233). The MB had no differences at E12.5 and had regressed in WT males by E17.5. The BC had no differences at E12.5, but at E17.5 had significant upregulation of Bdnf expression in ARKO, compared to WT males. There were no differences in CNTF or CNTF receptor expression.

Conclusions: Androgen alters active TrkB and Bdnf expression in the IFP. IFP Bdnf signalling may regulate "masculinisation" of the GFN sensory nerves to indirectly control inguinoscrotal testicular descent.

Impact: Androgen mediates neurotrophin release in the inguinal fat pad in mice, which may facilitate normal testicular descent by masculinising the GFN by peripheral uptake of neurotrophin. This is the first study to examine the role of neurotrophins in testicular descent. This suggests novel steps in the mechanical process of normal testicular descent that may be abnormal in some children with undescended testes.