Androgen promotes differentiation of PLZF+ spermatogonia pool via indirect regulatory pattern.

ABSTRACT: BACKGROUND:Androgen plays a pivotal role in spermatogenesis, accompanying a question how androgen acts on germ cells in testis since germ cells lack of androgen receptors (AR). Promyelocytic leukemia zinc-finger (PLZF) is essential for maintenance of undifferentiated spermatogonia population which is terminologically called spermatogonia progenitor cells (SPCs). AIMS:We aim to figure out the molecular connections between androgen and fates of PLZF+ SPCs population. METHOD:Immunohistochemistry was conducted to confirm that postnatal testicular germ cells lacked endogenous AR. Subsequently, total cells were isolated from 5 dpp (day post partum) mouse testes, and dihydrotestosterone (DHT) and/or bicalutamide treatment manifested that Plzf was indirectly regulated by androgen. Then, Sertoli cells were purified to screen downstream targets of AR using ChIP-seq, and gene silence and overexpression were used to attest these interactions in Sertoli cells or SPCs-Sertoli cells co-culture system. Finally, these connections were further verified in vivo using androgen pharmacological deprivation mouse model. RESULTS:Gata2 is identified as a target of AR, and ?1-integrin is a target of Wilms' tumor 1 (WT1) in Sertoli cells. Androgen signal negatively regulate ?1-integrin on Sertoli cells via Gata2 and WT1, and ?1-integrin on Sertoli cells interacts with E-cadherin on SPCs to regulate SPCs fates. CONCLUSION:Androgen promotes differentiation of PLZF+ spermatogonia pool via indirect regulatory pattern.

SUBMITTER: Wang J 

PROVIDER: S-EPMC6542041 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature