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. 2020 Apr 21;10:6751. doi: 10.1038/s41598-020-63290-3

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Model of spermatogenesis in WT and Sox3 KO adult testis. GFRα1 is found within the spermatogonial stem cell pool of WT testis, before being switched off as the cells progress into a progenitor cell state. Conversely, SOX3 is not found within the stem cell population and expression is switched on upon conversion into progenitor cells. SOX3 + progenitor cells differentiate and continue through the spermatogenesis pathway. Additional markers delineating the distinct differentiation stages of spermatogonia are indicated. In Sox3 knockout (KO) testis, the loss of SOX3 leads to an accumulation of GFRα1+ cells, and a reduction in the capacity to form differentiation-primed GFRα1- progenitor cells. This ultimately leads to a reduction in the production of differentiating spermatogonia. In adult WT testis, GFRα1+ stem cells are mostly present as A_s and A_pr while GFRα1+ A_al cells are frequently found in Sox3 null testis. Stem-progenitor transitional A_al cells expressing both GFRα1 and RARγ also accumulate in Sox3 knockouts but are rarely found in WT tubules. We propose that SOX3 plays an essential role in efficient stem to progenitor conversion within the undifferentiated spermatogonial population.