Androgen-mediated DGAT2 upregulation promotes ferroptosis in granulosa cells in polycystic ovary syn-drome
10.3969/j.issn.1006-5725.2025.16.009
- VernacularTitle:多囊卵巢综合征高雄激素介导二酰基甘油酰基转移酶2基因促进颗粒细胞铁死亡
- Author:
Yuancheng LI
1
;
Li LI
Author Information
1. 广州医科大学研究生院(广东 广州 511436);广东省妇幼保健院妇女儿童健康研究所(广东 广州 511400)
- Publication Type:Journal Article
- Keywords:
polycystic ovary syndrome;
DGAT2;
ferroptosis;
granulosa cells;
androgen
- From:
The Journal of Practical Medicine
2025;41(16):2498-2506
- CountryChina
- Language:Chinese
-
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.
