Regulation of nonylphenol-induced reproductive toxicity in mouse spermatogonia cells by miR-361-3p.

Nonylphenol (NP) is an environmental chemical that affects apoptosis and male infertility. In our study, we found that a high concentration of NP could down-regulate the expression of microRNA-361-3p (miR-361-3p) in the murine GC-1 spermatogonia cell line and in vivo in murine spermatogonia. Additionally, one direct target of this miR, the 3' untranslated region of Killin (Klln) mRNA, was identified. Klln encodes a transcription factor that directly regulates the expression of Tp73 (transcriptionally active p73), whose encoded protein can up-regulate the expression of Puma (p53 upregulated modulator of apoptosis). Thus, our investigation revealed that the expression of Klln, Tp73, and Puma increased upon NP-dependent down-regulation of miR-361-3p, which eventually leads to apoptosis of spermatogonia.