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. 2013 May 7;8(5):e63603. doi: 10.1371/journal.pone.0063603

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© 2013 Das et al

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.

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In DKDM, LRP6 becomes available because of diminished DKK3 levels. Available LRP6 binds to Frizzled receptor forming Fz-LRP6 complex augmenting WNT signaling. As a result, GSK-3β is recruited to Frizzled receptor reducing its availability for binding to β-CATENIN, thereby minimizing phosphorylation and degradation of β-CATENIN. Accumulated cytoplasmic β-CATENIN translocates to nucleus and augments expression of different genes, including that of itself, WNT4 and MIS in Sc. Elevated levels of MIS interferes with the Sc maturation, hence, disturbing the balance between spermatogonial proliferation and differentiation leading to subfertility and/or infertility. Additionally, MIS is known to inhibit T production via suppression of CYP17 activity in Lc which might be the reason for reduced T levels in such mice. (eS-elongated spermatids, SSC-spermatogonial stem cells, Fz-Frizzled, rS-round spermatid, SpC-spermatocytes, PTc-peritubular cell, Tcf/Lcf -transcription factors).