Androgen-mediated DGAT2 upregulation promotes ferroptosis in granulosa cells in polycystic ovary syn-drome
LI Yuancheng
LI Li
Abstract：Objective To investigate the role of androgen-induced DGAT2-mediated ferroptosis in granu-losa cell dysfunction in patients with polycystic ovary syndrome(PCOS).Methods The human granulosa cell line KGN was exposed to various concentrations of testosterone(1,10,and 100 μmol/L).The effects on DGAT2 expres-sion,markers of ferroptosis(GPX4,ROS,MDA),indicators of lipid metabolism(TG,PUFAs),lipid droplet ac-cumulation,and cell viability were evaluated.Additionally,DGAT2 knockdown using siRNA in combination with Erastin treatment was performed to further elucidate the role of DGAT2 in ferroptosis regulation.Results Testoster-one significantly upregulated DGAT2 expression(P<0.01),increased intracellular TG and PUFA levels(P<0.001),promoted lipid droplet accumulation,elevated ROS and MDA levels(P<0.05,P<0.001),suppressed GPX4 expression(P<0.001),and reduced cell viability(P<0.001).DGAT2 knockdown reversed these effects,thereby alleviating ferroptosis and markedly enhancing cell viability(P<0.001).Conclusions DGAT2 may be in-volved in the process of androgen-mediated granulosa cell ferroptosis in patients with PCOS.
Keywords：polycystic ovary syndromeDGAT2ferroptosisgranulosa cellsandrogen
Publication Date：2025-08-25
Online Publishing Date：2025-09-04(First online date of this platform, not the publication date of the document)
Pages：9( 2498-2506 )