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

doi:10.3969/j.issn.1006-5725.2025.16.009

Abstract

Abstract:

Objective To investigate the role of androgen-induced DGAT2-mediated ferroptosis in granulosa 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 expression， markers of ferroptosis （GPX4， ROS， MDA）， indicators of lipid metabolism （TG， PUFAs）， lipid droplet accumulation， 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 Testosterone 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 involved in the process of androgen-mediated granulosa cell ferroptosis in patients with PCOS.

Key words: polycystic ovary syndrome, DGAT2, ferroptosis, granulosa cells, androgen

CLC Number:

R711.51

Yuancheng LI,Li. LI. Androgen‑mediated DGAT2 upregulation promotes ferroptosis in granulosa cells in polycystic ovary syndrome[J]. The Journal of Practical Medicine, 2025, 41(16): 2498-2506.

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References 22

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引物名称	RNA类型	序列	纯化方法	修饰
hDGAT2-459-s	双链	GGAACUAUAUCUUUGGAUA/dT//dT/	HPLC	DNA-T
hDGAT2-459-a	双链	UAUCCAAAGAUAUAGUUCC/dT//dT/	HPLC	DNA-T

目的基因	正向引物	反向引物
DGAT2	GAATGGGAGTGGCAATGCTAT	CCTCGAAGATCACCTGCTTGT
GPX4	GAGGCAAGACCGAAGTAAACTAC	CCGAACTGGTTACACGGGAA
GAPDH	GGAGCGAGATCCCTCCAAAAT	GGCTGTTGTCATACTTCTCATGG

基因名称	相对表达量				F值	P值
基因名称	Ctrl组	1 μmol/L T组	10 μmol/L T组	100 μmol/L T组	F值	P值
DGAT2	0.973 ± 0.431	1.114 ± 0.122^*	1.701 ± 0.328^***	2.849 ± 0.523^***	73.275	< 0.05
GPX4	1.003 ± 0.102	0.668 ± 0.272	0.561 ± 0.268^*	1.376 ± 0.358	13.316	< 0.001

组别	相对荧光强度	F值	P值
Ctrl组	1.000 ± 0.056	5.825	> 0.05
10 μmol/L T组	1.594 ± 0.134^**	5.825	> 0.05

Androgen‑mediated DGAT2 upregulation promotes ferroptosis in granulosa cells in polycystic ovary syndrome

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