Cypermethrin inhibits proliferation of Sertoli cells through AR involving DAB2IP/PI3K/AKT signaling pathway in vitro

Qi Wang; Xu-Xu Wang; Jia-Fei Xie; Ting-Ting Yao; Lin-Lin Xu; Lu-Shan Wang; Yue Yu; Li-Chun Xu

doi:10.1093/toxres/tfac037

Cypermethrin inhibits proliferation of Sertoli cells through AR involving DAB2IP/PI3K/AKT signaling pathway in vitro

Toxicol Res (Camb). 2022 Jun 10;11(4):583-591. doi: 10.1093/toxres/tfac037. eCollection 2022 Aug.

Authors

Qi Wang^{1

2}, Xu-Xu Wang^{1

2}, Jia-Fei Xie^{1

2}, Ting-Ting Yao^{1

2}, Lin-Lin Xu^{1

2}, Lu-Shan Wang^{1

2}, Yue Yu^{1

2}, Li-Chun Xu^{1

2}

Affiliations

¹ Key Lab of Environment and Health, School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu 221004, China.
² Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.

Abstract

Cypermethrin (CP) exhibits anti-androgenic effects through antagonism on androgen receptor (AR) activation. This study was to identify whether AR-mediated disabled 2 interacting protein (DAB2IP)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway was involved in CP-induced mouse Sertoli cells (TM4) proliferation disorder. Real-Time Cell Analysis-iCELLigence system was to measure cell proliferation. Bioinformatic analyses were performed to identify AR-regulated genes. Quantitative Real-Time PCR and western blot were to detect the genes and proteins levels in AR-mediated DAB2IP/PI3K/AKT pathway. Results showed CP suppressed TM4 proliferation and the expression of AR. Activation of AR restored the inhibition efficacy of CP on TM4 proliferation. AR regulated DAB2IP expression and phosphorylation levels of PI3K and AKT in CP-exposed TM4 cells. In addition, knockdown of DAB2IP alleviated the inhibition efficacy of CP on cell proliferation and phosphorylation of PI3K and AKT. Taken together, AR was a modulator in CP-induced inhibition of Sertoli cells proliferation by negatively regulating DAB2IP/PI3K/AKT signaling pathway. The study may provide a new insight for the mechanisms of male reproductive toxicity induced by CP.

Keywords: DAB2IP/PI3K/AKT signaling pathway; Sertoli cells; androgen receptor; cypermethrin.