Menopause Mysteries: the Exosome-inflammation Connection

Overview

Journal J Ovarian Res

Publisher Biomed Central

Date 2025 Jan 24

PMID 39849635

Authors

Aarushi Sultania

Subhashini Brahadeeswaran

Aparna Eledath Kolasseri

Sivaraman Jayanthi

Ramasamy Tamizhselvi

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles, or exosomes, are produced by every type of cell and contain metabolites, proteins, lipids, and nucleic acids. Their role in health and disease is to influence different aspects of cell biology and to act as intermediaries between cells. Follicular fluid exosomes or extracellular vesicles (FF-EVs) secreted by ovarian granulosa cells are critical mediators of ovary growth and maturation. The movement and proteins of these exosomes are crucial in the regulation of cellular communication and the aging of cells, a process termed inflammaging. Menopause, a natural progression in the aging of females, is often accompanied by numerous negative symptoms and health issues. It can also act as a precursor to more severe health problems, including neurological, cardiovascular, and metabolic diseases, as well as gynecological cancers. Researchers have discovered pathways that reveal the diverse effects of exosome-driven cellular communication and oocyte development in the follicular fluid. It also explores the complex functions of FF exosomal proteins in the pathologies associated with menopause.

References

Marconi G, Diomede F, Trubiani O, Porcheri C, Mitsiadis T . Exosomes as Carriers for Notch Molecules. Methods Mol Biol. 2022; 2472:197-208. DOI: 10.1007/978-1-0716-2201-8_16. View

Uzbekova S, Alminana C, Labas V, Teixeira-Gomes A, Combes-Soia L, Tsikis G . Protein Cargo of Extracellular Vesicles From Bovine Follicular Fluid and Analysis of Their Origin From Different Ovarian Cells. Front Vet Sci. 2020; 7:584948. PMC: 7672127. DOI: 10.3389/fvets.2020.584948. View

Russell M, Cowan R, Harman R, Walker A, Quirk S . The hedgehog signaling pathway in the mouse ovary. Biol Reprod. 2007; 77(2):226-36. DOI: 10.1095/biolreprod.106.053629. View

Vanorny D, Mayo K . The role of Notch signaling in the mammalian ovary. Reproduction. 2017; 153(6):R187-R204. PMC: 5512555. DOI: 10.1530/REP-16-0689. View

Yan F, Zhao Q, Li Y, Zheng Z, Kong X, Shu C . The role of oxidative stress in ovarian aging: a review. J Ovarian Res. 2022; 15(1):100. PMC: 9434839. DOI: 10.1186/s13048-022-01032-x. View

McCarthy M, Raval A . The peri-menopause in a woman's life: a systemic inflammatory phase that enables later neurodegenerative disease. J Neuroinflammation. 2020; 17(1):317. PMC: 7585188. DOI: 10.1186/s12974-020-01998-9. View

Zhang Y, Liu Y, Liu H, Tang W . Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci. 2019; 9:19. PMC: 6377728. DOI: 10.1186/s13578-019-0282-2. View

Dupont J, Scaramuzzi R . Insulin signalling and glucose transport in the ovary and ovarian function during the ovarian cycle. Biochem J. 2016; 473(11):1483-501. PMC: 4888492. DOI: 10.1042/BCJ20160124. View

Gong Y, Li-Ling J, Xiong D, Wei J, Zhong T, Tan H . Age-related decline in the expression of GDF9 and BMP15 genes in follicle fluid and granulosa cells derived from poor ovarian responders. J Ovarian Res. 2021; 14(1):1. PMC: 7780377. DOI: 10.1186/s13048-020-00757-x. View

10.

Patton B, Madadi S, Pangas S . Control of ovarian follicle development by TGFβ family signaling. Curr Opin Endocr Metab Res. 2021; 18:102-110. PMC: 8535782. DOI: 10.1016/j.coemr.2021.03.001. View

11.

Chen X, Luo Y, Zhu Q, Zhang J, Huang H, Kan Y . Small extracellular vesicles from young plasma reverse age-related functional declines by improving mitochondrial energy metabolism. Nat Aging. 2024; 4(6):814-838. PMC: 11186790. DOI: 10.1038/s43587-024-00612-4. View

12.

Boyer A, Lapointe E, Zheng X, Cowan R, Li H, Quirk S . WNT4 is required for normal ovarian follicle development and female fertility. FASEB J. 2010; 24(8):3010-25. PMC: 2909279. DOI: 10.1096/fj.09-145789. View

13.

Liu Y, Mu H, Chen Y, Li K, Mei Q, Wang L . Follicular fluid-derived exosomes rejuvenate ovarian aging through miR-320a-3p-mediated FOXQ1 inhibition. Life Med. 2025; 3(1):lnae013. PMC: 11749233. DOI: 10.1093/lifemedi/lnae013. View

14.

Templeman N, Cota V, Keyes W, Kaletsky R, Murphy C . CREB Non-autonomously Controls Reproductive Aging through Hedgehog/Patched Signaling. Dev Cell. 2020; 54(1):92-105.e5. PMC: 7837322. DOI: 10.1016/j.devcel.2020.05.023. View

15.

Shah D, Rasool S . Polycystic Ovary Syndrome (PCOS) Transition at Menopause. J Midlife Health. 2021; 12(1):30-32. PMC: 8189337. DOI: 10.4103/jmh.jmh_37_21. View

16.

Hernandez Borrero L, El-Deiry W . Tumor suppressor p53: Biology, signaling pathways, and therapeutic targeting. Biochim Biophys Acta Rev Cancer. 2021; 1876(1):188556. PMC: 8730328. DOI: 10.1016/j.bbcan.2021.188556. View

17.

Li L, Shi X, Shi Y, Wang Z . The Signaling Pathways Involved in Ovarian Follicle Development. Front Physiol. 2021; 12:730196. PMC: 8504451. DOI: 10.3389/fphys.2021.730196. View

18.

Feng Z . p53 regulation of the IGF-1/AKT/mTOR pathways and the endosomal compartment. Cold Spring Harb Perspect Biol. 2010; 2(2):a001057. PMC: 2828273. DOI: 10.1101/cshperspect.a001057. View

19.

Gebremedhn S, Ali A, Hossain M, Hoelker M, Salilew-Wondim D, Anthony R . MicroRNA-Mediated Gene Regulatory Mechanisms in Mammalian Female Reproductive Health. Int J Mol Sci. 2021; 22(2). PMC: 7832875. DOI: 10.3390/ijms22020938. View

20.

Steven A, Friedrich M, Jank P, Heimer N, Budczies J, Denkert C . What turns CREB on? And off? And why does it matter?. Cell Mol Life Sci. 2020; 77(20):4049-4067. PMC: 7532970. DOI: 10.1007/s00018-020-03525-8. View