The Journal of Practical Medicine >

2025 , Vol. 41 >Issue 16: 2498 - 2506

DOI: https://doi.org/10.3969/j.issn.1006-5725.2025.16.009

Basic Research

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

  • Yuancheng LI ,
  • Li. LI
Expand
  • Graduate School of Guangzhou Medical University，Guangzhou 511436，Guangdong，China；Women and Children's Health Research Institute of Guangdong Provincial Maternal and Child Health Hospital，Guangzhou 511400，Guangdong，China

Received date: 2025-04-19

  Online published: 2025-08-28

Fold

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

Cite this article

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 . DOI: 10.3969/j.issn.1006-5725.2025.16.009

References

[1] SUTURINA L， LIZNEVA D， LAZAREVA L， et al. Ethnicity and the Prevalence of Polycystic Ovary Syndrome： The Eastern Siberia PCOS Epidemiology and Phenotype Study［J］. J Clin Endocrinol Metab， 2024，110（1）：e32-e43. doi:10.1210/clinem/dgae530
[2] TEEDE H J， TAY C T， LAVEN J J E， et al. Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome［J］. Eur J Endocrinol， 2023， 189（2）：G43-G64. doi:10.1097/OGX.0000000000001233
[3] STENER-VICTORIN E， TEEDE H， NORMAN R J， et al. Polycystic ovary syndrome［J］. Nat Rev Dis Primers， 2024， 10（1）：27. doi:10.1038/s41572-024-00511-3
[4] 李荔，周嘉禾，李末娟，等.多囊卵巢综合征表观遗传学、代谢组学、肠道菌群新机制前沿展望［J］.实用医学杂志，2022，38（16）：1987-1992. doi:10.3969/j.issn.1006-5725.2022.16.001
[5] 吴妍芝，刘洋.m6A修饰在良性卵巢相关疾病的研究进展［J］.实用医学杂志，2024，40（16）：2352-2356. doi:10.3969/j.issn.1006-5725.2024.16.024
[6] ZHANG C， LI Y， WANG Y， et al. Genetic associations of metabolic factors and therapeutic drug targets with polycystic ovary syndrome［J］. J Adv Res， 2024. doi： 10.1016/j.jare.2024.10.038 . Epub ahead of print.
[7] STRINGER J M， ALESI L R， WINSHIP A L， et al. Beyond apoptosis： Evidence of other regulated cell death pathways in the ovary throughout development and life［J］. Hum Reprod Update， 2023，29（4）：434-456. doi:10.1093/humupd/dmad005
[8] CALLE R A， AMIN N B， CARVAJAL-GONZALEZ S， et al. ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease： Two parallel， placebo-controlled， randomized phase 2a trials［J］. Nat Med， 2021，27（10）：1836-1848. doi:10.1038/s41591-021-01489-1
[9] RONG S， XIA M， VALE G， et al. DGAT2 inhibition blocks SREBP-1 cleavage and improves hepatic steatosis by increasing phosphatidylethanolamine in the ER［J］. Cell Metab， 2024，36（3） ：617-629.e7. doi:10.1016/j.cmet.2024.01.011
[10] GHIMIRE J， COLLINS M E， SNARSKI P， et al. Obesity-Facilitated Colon Cancer Progression Is Mediated by Increased Diacylglycerol O-Acyltransferases 1 and 2 Levels［J］. Gastroenterology， 2025，168（2） ：286-299.e6. doi:10.1053/j.gastro.2024.09.011
[11] FRIEDMANN ANGELI J P， SCHNEIDER M， PRONETH B， et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice［J］.Nat Cell Biol， 2014， 16， 1180-1191. doi:10.1038/ncb3064
[12] GUO K， LU M， BI J， et al. Ferroptosis： Mechanism， immunotherapy and role in ovarian cancer［J］.Front Immunol， 2024，15：1410018. doi:10.3389/fimmu.2024.1410018
[13] JIANG X， STOCKWELL B R， CONRAD M. Ferroptosis： Mechanisms， biology and role in disease［J］.Nat Rev Mol Cell Biol， 2021，22（4）：266-282. doi:10.1038/s41580-020-00324-8
[14] LEI G， ZHUANG L， GAN B. Targeting ferroptosis as a vulnerability in cancer［J］. Nat Rev Cancer， 2022，22（7）：381-396. doi:10.1038/s41568-022-00459-0
[15] LIU M， WU K， WU Y. The emerging role of ferroptosis in female reproductive disorders［J］. Biomed Pharmacother， 2023， 166：115415. doi:10.1016/j.biopha.2023.115415
[16] LI X， LIN Y， CHENG X， et al. Ovarian ferroptosis induced by androgen is involved in pathogenesis of PCOS［J］. Hum Reprod Open， 2024， 2024（2）：hoae013. doi:10.1093/hropen/hoae013
[17] YAN H， WANG L， ZHANG G， et al. Oxidative stress and energy metabolism abnormalities in polycystic ovary syndrome： From mechanisms to therapeutic strategies［J］. Reprod Biol Endocrinol， 2024， 22（1）：159. doi:10.1186/s12958-024-01337-0
[18] YEN C E， STONE S J， KOLIWAD S， et al. Thematic review series： Glycerolipids. DGAT enzymes and triacylglycerol biosynthesis［J］. J Lipid Res， 2008，49（11）：2283-2301. doi:10.1194/jlr.r800018-jlr200
[19] LOOMBA R， MORGAN E， WATTS L， et al. Novel antisense inhibition of diacylglycerol O-acyltransferase 2 for treatment of non-alcoholic fatty liver disease： A multicentre， double-blind， randomised， placebo-controlled phase 2 trial［J］. Lancet Gastroenterol Hepatol， 2020，5（9）：829-838. doi:10.1016/s2468-1253(20)30186-2
[20] HUDDLESTON H G， DOKRAS A. Diagnosis and Treatment of Polycystic Ovary Syndrome［J］. JAMA， 2022， 327： 274-275. doi:10.1001/jama.2021.23769
[21] IPSEN D H， LYKKESFELDT J， TVEDEN-NYBORG P. Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease［J］. Cell Mol Life Sci， 2018，75（18）：3313-3327. doi:10.1007/s00018-018-2860-6
[22] LEI S， CHEN C， HAN F， et al. AMER1 deficiency promotes the distant metastasis of colorectal cancer by inhibiting SLC7A11- and FTL-mediated ferroptosis［J］. Cell Rep， 2023，42（9）：113110. doi:10.1016/j.celrep.2023.113110
Options
Outlines

/

〈 〉