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Androgen Promotes Differentiation of PLZF+ Spermatogonia pool via Indirect Regulatory Pattern

By Jingjing Wang, Jinmei Li, Yunzhao Gu, Qin Xia, Weixiang Song, Xiaoyu Zhang, Yang Yang, Wei Wang, Hua Li, Kang Zou

Posted 09 Apr 2018
bioRxiv DOI: 10.1101/297846 (published DOI: 10.1186/s12964-019-0369-8)

Androgen signaling plays a pivotal role in spermatogenesis, but the molecular mechanisms underlying androgen action in this process are unclear. Specifically, it is unknown if the androgen receptor (AR) is expressed in germ cells. Thus it's interesting to reveal how androgen induces differentiation of spermatogonial progenitor cells (SPCs) in the niche. Here we observed the AR is primarily expressed in pre-spermatogonia of mice 2 days post partum (dpp), absent before spermatogenesis onset, and then expressed in surrounding Sertoli cells. Then we examined a regulatory role of the AR in spermatogenesis using a SPCs-Sertoli cells co-culture system, and demonstrated that androgen negatively regulated Plzf ( the gene for stemness maintenance of SPCs). Additionally, we identified Gata2 as a target of AR in Sertoli cells, and demonstrated that Wilms tumor 1 (WT1) and β1-integrin as two putative intermediate molecules to transfer differentiation signals to SPCs, which was further verified using androgen pharmacological-deprivation mice model. These results demonstrate a regulatory pattern of androgen in SPCs niche in an indirect way via multiple steps of signal transduction.

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