Mitochondrial Abnormality in Ovarian Granulosa Cells of Patients with Polycystic Ovary Syndrome

Overview

Journal Mol Med Rep

Specialty Molecular Biology

Date 2023 Dec 22

PMID 38131196

Authors

Congcong Xie

Hui Lu

Xiujia Zhang

Zhuo An

Tong Chen

Wenbo Yu

Shusong Wang

Dandan Shang

Xueying Wang

Affiliations

Soon will be listed here.

Abstract

The quality of oocytes in patients with polycystic ovary syndrome (PCOS) decreases, which is closely related to the function of oocytes' mitochondria. If mitochondrial dysfunction is involved in PCOS, it is likely to affect the function of cumulus cells. However, the mechanism of mitochondrial dysfunction remains unclear. In the present study, granulosa cells were collected from women attending the Hebei Reproductive Health Hospital and were divided into the normal ovarian reserve group (CON group) and the PCOS group. The mitochondrial ultrastructure was observed by transmission electron microscope, and the mitochondrial function was determined by detecting the ATP content, reactive oxygen species levels, the number of mitochondria and the mitochondrial membrane potential. Additionally, western blotting was used to compare the expression levels of mitochondrial kinetic protein, the related channel protein, between the two groups. In the present study, it was found that patients with PCOS had abnormal granulosa cell morphology, increased mitochondrial abnormalities, decreased mitochondrial function and disturbed mitochondrial dynamics. In addition, the silent information regulator 1/phosphorylated‑AMP‑activated protein kinase/peroxisome proliferator‑activated receptor‑γ coactivator 1α pathway expression was decreased, and it was hypothesized that the decreased mitochondrial mass in the PCOS group was associated with it.

Citing Articles

Melatonin refines ovarian mitochondrial dysfunction in PCOS by regulating the circadian rhythm gene Clock.

Chen W, Zhang H, Guo B, Tao Y, Zhang J, Wang J Cell Mol Life Sci. 2025; 82(1):104.

PMID: 40047877 PMC: 11885701. DOI: 10.1007/s00018-025-05609-9.

Transcriptomic analysis of the effects exerted by curcumin on dihydrotestosterone-induced ovarian granulosa cells.

Chen D, Yu Q, Sheng S, Cai L, Zheng J, Zhang Y Front Endocrinol (Lausanne). 2025; 16:1522269.

PMID: 40017688 PMC: 11864909. DOI: 10.3389/fendo.2025.1522269.

Oxidative stress and energy metabolism abnormalities in polycystic ovary syndrome: from mechanisms to therapeutic strategies.

Yan H, Wang L, Zhang G, Li N, Zhao Y, Liu J Reprod Biol Endocrinol. 2024; 22(1):159.

PMID: 39722030 PMC: 11670460. DOI: 10.1186/s12958-024-01337-0.

The P38MAPK Pathway Mediates the Destruction of the Blood-Brain Barrier in Anti-NMDAR Encephalitis Mice.

Lao D, Gong Z, Li T, Mo X, Huang W Neurochem Res. 2024; 50(1):21.

PMID: 39560818 PMC: 11576659. DOI: 10.1007/s11064-024-04270-1.

Granulosa cell insight: unraveling the potential of menstrual blood-derived stem cells and their exosomes on mitochondrial mechanisms in polycystic ovary syndrome (PCOS).

Mansoori M, Solhjoo S, Palmerini M, Nematollahi-Mahani S, Ezzatabadipour M J Ovarian Res. 2024; 17(1):167.

PMID: 39153978 PMC: 11330151. DOI: 10.1186/s13048-024-01484-3.

References

Yefimova M, Lefevre C, Bashamboo A, Eozenou C, Burel A, Lavault M . Granulosa cells provide elimination of apoptotic oocytes through unconventional autophagy-assisted phagocytosis. Hum Reprod. 2020; 35(6):1346-1362. DOI: 10.1093/humrep/deaa097. View

Richani D, Dunning K, Thompson J, Gilchrist R . Metabolic co-dependence of the oocyte and cumulus cells: essential role in determining oocyte developmental competence. Hum Reprod Update. 2020; 27(1):27-47. DOI: 10.1093/humupd/dmaa043. View

Liu Y, Han M, Li X, Wang H, Ma M, Zhang S . Age-related changes in the mitochondria of human mural granulosa cells. Hum Reprod. 2017; 32(12):2465-2473. DOI: 10.1093/humrep/dex309. View

Wang C, Liu T, Tong Y, Cui R, Qu K, Liu C . Ulinastatin protects against acetaminophen-induced liver injury by alleviating ferroptosis via the SIRT1/NRF2/HO-1 pathway. Am J Transl Res. 2021; 13(6):6031-6042. PMC: 8290678. View

Kalia R, Wang R, Yusuf A, Thomas P, Agard D, Shaw J . Structural basis of mitochondrial receptor binding and constriction by DRP1. Nature. 2018; 558(7710):401-405. PMC: 6120343. DOI: 10.1038/s41586-018-0211-2. View

Guijarro L, Cano-Martinez D, Toledo-Lobo M, Ruiz-Llorente L, Chaparro M, Guerra I . Evaluation of AIF-1 (Allograft Inflammatory Factor-1) as a Biomarker of Crohn's Disease Severity. Biomedicines. 2022; 10(3). PMC: 8945466. DOI: 10.3390/biomedicines10030727. View

Chiang J, Shukla P, Pagidas K, Ahmed N, Karri S, Gunn D . Mitochondria in Ovarian Aging and Reproductive Longevity. Ageing Res Rev. 2020; 63:101168. PMC: 9375691. DOI: 10.1016/j.arr.2020.101168. View

Hao L, Zhong W, Dong H, Guo W, Sun X, Zhang W . ATF4 activation promotes hepatic mitochondrial dysfunction by repressing NRF1-TFAM signalling in alcoholic steatohepatitis. Gut. 2020; 70(10):1933-1945. PMC: 8110597. DOI: 10.1136/gutjnl-2020-321548. View

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

10.

Guo A, Li K, Xiao Q . Fibroblast growth factor 19 alleviates palmitic acid-induced mitochondrial dysfunction and oxidative stress via the AMPK/PGC-1α pathway in skeletal muscle. Biochem Biophys Res Commun. 2020; 526(4):1069-1076. DOI: 10.1016/j.bbrc.2020.04.002. View

11.

Patil K, Shinde G, Hinduja I, Mukherjee S . Compromised Cumulus-Oocyte Complex Matrix Organization and Expansion in Women with PCOS. Reprod Sci. 2021; 29(3):836-848. DOI: 10.1007/s43032-021-00775-0. View

12.

Emidio G, Placidi M, Rea F, Rossi G, Falone S, Cristiano L . Methylglyoxal-Dependent Glycative Stress and Deregulation of SIRT1 Functional Network in the Ovary of PCOS Mice. Cells. 2020; 9(1). PMC: 7017084. DOI: 10.3390/cells9010209. View

13.

Guijarro L, Sanmartin-Salinas P, Perez-Cuevas E, Toledo-Lobo M, Monserrat J, Zoullas S . Actinomycin D Arrests Cell Cycle of Hepatocellular Carcinoma Cell Lines and Induces p53-Dependent Cell Death: A Study of the Molecular Mechanism Involved in the Protective Effect of IRS-4. Pharmaceuticals (Basel). 2021; 14(9). PMC: 8472101. DOI: 10.3390/ph14090845. View

14.

Tian L, Cao W, Yue R, Yuan Y, Guo X, Qin D . Pretreatment with Tilianin improves mitochondrial energy metabolism and oxidative stress in rats with myocardial ischemia/reperfusion injury via AMPK/SIRT1/PGC-1 alpha signaling pathway. J Pharmacol Sci. 2019; 139(4):352-360. DOI: 10.1016/j.jphs.2019.02.008. View

15.

Zhao Y, Zhang J, Zheng Y, Zhang Y, Zhang X, Wang H . NAD improves cognitive function and reduces neuroinflammation by ameliorating mitochondrial damage and decreasing ROS production in chronic cerebral hypoperfusion models through Sirt1/PGC-1α pathway. J Neuroinflammation. 2021; 18(1):207. PMC: 8444613. DOI: 10.1186/s12974-021-02250-8. View

16.

Yapa N, Lisnyak V, Reljic B, Ryan M . Mitochondrial dynamics in health and disease. FEBS Lett. 2021; 595(8):1184-1204. DOI: 10.1002/1873-3468.14077. View

17.

Maremanda K, Sundar I, Rahman I . Role of inner mitochondrial protein OPA1 in mitochondrial dysfunction by tobacco smoking and in the pathogenesis of COPD. Redox Biol. 2021; 45:102055. PMC: 8258692. DOI: 10.1016/j.redox.2021.102055. View

18.

Lai Q, Xiang W, Li Q, Zhang H, Li Y, Zhu G . Oxidative stress in granulosa cells contributes to poor oocyte quality and IVF-ET outcomes in women with polycystic ovary syndrome. Front Med. 2017; 12(5):518-524. DOI: 10.1007/s11684-017-0575-y. View

19.

Kalliora C, Kyriazis I, Oka S, Lieu M, Yue Y, Area-Gomez E . Dual peroxisome-proliferator-activated-receptor-α/γ activation inhibits SIRT1-PGC1α axis and causes cardiac dysfunction. JCI Insight. 2019; 5. PMC: 6777908. DOI: 10.1172/jci.insight.129556. View

20.

Sun L, Tian H, Xue S, Ye H, Xue X, Wang R . Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary Syndrome. Front Cell Dev Biol. 2021; 9:658112. PMC: 8374745. DOI: 10.3389/fcell.2021.658112. View