Molecular mechanism of sterilization by quinestrol, a rodent sterility control agent

Sterility control is one of the key tools for regulating pest rodent population density. An in-depth analysis of the molecular mechanism of sterility caused by control agents is of great significance for further exploration of novel sterility controls and the development of alternative drugs. In this study, male plateau zokors (Eospalax baileyi) in the breeding period were used as research subject to explore the molecular mechanism of quinestrol-induced sterility. We used RNA-seq technology to investigate key genes and signaling pathways associated with the inhibition of testicular development and spermatogenesis, and validated these findings through qPCR. The findings indicated that in plateau zokors treated with quinestrol, 420 genes were down-regulated and 127 genes were up-regulated. Notch3, Ppp2r3c, Lipe, Il1b, and Tlr2 are the potential new targets for quinestrol to affect testicular development in plateau zokors. GO analysis showed that DEGs were enriched in the inflammatory response, positive regulation of ERK1 and ERK2 cascades and positive regulation of MAPK cascades. KEGG analysis showed that DEGs were enriched in pathways such as metabolism of xenobiotics by cytochrome P450. GSEA analysis revealed that treatment with quinestrol induced pathways-related changes related to the positive regulation of the ERK1 and ERK2 cascades and the positive regulation of PI3K/AKT signaling in plateau zokors. Quinestrol influences the ERK1/2 signaling pathway within the MAPK cascade in spermatogonia of plateau zokor testes via the GPER1 receptor, inducing oxidative stress and resulting in male infertility.