Perfluorooctane sulfonate (PFOS) induces apoptosis and autophagy by inhibition of PI3K/AKT/mTOR pathway in human granulosa cell line KGN

Abstract

Perfluorooctane sulfonate (PFOS) is recognized as an environmental endocrine disruptor with widespread use in industrial manufacturing and daily life, contributing to various public health concerns. However, the precise impacts of PFOS on the ovary and its regulatory mechanisms remain unclear. This study aims to delineate the ovarian toxicity of PFOS and scrutinize its effects on apoptosis and autophagy through modulation of the PI3K/AKT/mTOR pathway in the human granulosa cell line (KGN). Cell viability, assessed via the Cell Counting Kit-8 (CCK8), revealed a dose-dependent reduction in cell viability upon PFOS exposure. Flow cytometry analysis demonstrated an elevated proportion of apoptotic cells following PFOS treatment. Western blot analyses unveiled increased expression of Bax, Cyt c, cleaved caspase-9, and LC3-II/I, coupled with decreased expression of Bcl-2 and p62. Transmission electron microscopy (TEM) observations illustrated a heightened number of autophagosomes induced by PFOS. Molecular docking investigations, in conjunction with Western blot experiments, substantiated PFOS's significant inhibition of the PI3K/AKT/mTOR signaling pathway. These findings collectively underscore that PFOS induces apoptosis and autophagy in KGN cells through modulation of the PI3K/AKT/mTOR pathway, providing experimental evidence for PFOS-induced ovarian toxicity and elucidating the underlying regulatory mechanisms in KGN cells.