The differentiation of germ cells into oogonia or spermatogonia is the first step that eventually gives rise to fully mature gametes. In the female fetal gonad, the RSPO1/WNT/CTNNB1 signalling pathway is involved in primordial germ cell proliferation and differentiation into female germ cells, which are able to enter meiosis. In the postnatal testis, the WNT/CTNNB1 pathway also mediates proliferation of spermatogonial stem cells and progenitor cells. Here we show that forced activation of the WNT/CTNNB1 pathway in fetal gonocytes using transgenic mice leads to deregulated spermatogonial proliferation, and exhaustion of the spermatocytes by apoptosis, resulting in a hypoplastic testis. These findings demonstrate that a finely tuned timing in WNT/CTNNB1 signalling activity is required for spermatogenesis.
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