GRSF1 deficiency attenuates mitochondrial function in aging granulosa cells

in Reproduction
Authors:
Canxin Wen Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health,Shandong University, Jinan, Shandong, China
Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China

Search for other papers by Canxin Wen in
Current site
Google Scholar
PubMed Close
,
Linlin Jiang Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China

Search for other papers by Linlin Jiang in
Current site
Google Scholar
PubMed Close
,
Ping Pan Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China

Search for other papers by Ping Pan in
Current site
Google Scholar
PubMed Close
,
Jia Huang Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China

Search for other papers by Jia Huang in
Current site
Google Scholar
PubMed Close
,
Yanxin Xie Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China

Search for other papers by Yanxin Xie in
Current site
Google Scholar
PubMed Close
,
Songbang Ou Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China

Search for other papers by Songbang Ou in
Current site
Google Scholar
PubMed Close
, and
Yu Li Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, Guangzhou, China

Search for other papers by Yu Li in
Current site
Google Scholar
PubMed Close
https://orcid.org/0000-0002-8580-0319

Correspondence should be addressed to Y Li; Email: liyu7@mail.sysu.edu.cn

*(C Wen and L Jiang contributed equally to this work)

DOI:
https://doi.org/10.1530/REP-24-0015
Volume/Issue:
Volume 168: Issue 2
Article ID:
e240015
Article Type:
Research Article
Online Publication Date:
21 Jun 2024
Copyright:
© the author(s) 2024
Restricted access
Rent on DeepDyve

Sign up for journal news

In brief

Ovarian aging results in reactive oxygen species accumulation and mitochondrial deterioration. During the aging process, GRSF1 deficiency attenuates mitochondrial function in aging granulosa cells.

Abstract

Ovarian aging critically influences reproductive potential, with a marked decrease in oocyte quality and quantity and an increase in oxidative stress and mitochondrial dysfunction. This study elucidates the role of guanine-rich RNA sequence binding factor 1 (GRSF1) in the aging of ovarian granulosa cells (GCs). We observed a significant reduction in GRSF1 within GCs correlating with patient age, utilizing clinical samples from IVF patients. Using an siRNA-mediated knockdown technique, we established that diminished GRSF1 expression exacerbates mitochondrial dysfunction, elevates reactive oxygen species, and impairs ATP production. Furthermore, RNA immunoprecipitation revealed GRSF1’s interaction with superoxide dismutase 2 (SOD2) mRNA, a key antioxidant enzyme, suggesting a mechanism whereby GRSF1 modulates oxidative stress. Downregulation of SOD2 reversed the protective effects of GRSF1 overexpression on mitochondrial function. These insights into the role of GRSF1 in ovarian aging may guide the development of interventions to improve fertility outcomes in advanced age.

Reproduction is committed to supporting researchers in demonstrating the impact of their articles published in the journal.

The two types of article metrics we measure are (i) more traditional full-text views and pdf downloads, and (ii) Altmetric data, which shows the wider impact of articles in a range of non-traditional sources, such as social media.

More information is on the Reasons to publish page.

Sept 2018 onwards Past Year Past 30 Days
Full Text Views 210 199 10
PDF Downloads 154 140 14

 

  • Collapse
  • Expand
Print ISSN:
1470-1626
Online ISSN:
1741-7899

  • Antonicka H, Sasarman F, Nishimura T, Paupe V & & Shoubridge EA 2013 The mitochondrial RNA-binding protein GRSF1 localizes to RNA granules and is required for posttranscriptional mitochondrial gene expression. Cell Metabolism 17 386–398. (https://doi.org/10.1016/j.cmet.2013.02.006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bedrat A, Lacroix L & & Mergny JL 2016 Re-evaluation of G-quadruplex propensity with G4Hunter. Nucleic Acids Research 44 1746–1759. (https://doi.org/10.1093/nar/gkw006)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ben-Meir A, Burstein E, Borrego-Alvarez A, Chong J, Wong E, Yavorska T, Naranian T, Chi M, Wang Y & Bentov Y et al.2015 Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging. Aging Cell 14 887–895. (https://doi.org/10.1111/acel.12368)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bentov Y & & Casper RF 2013 The aging oocyte–can mitochondrial function be improved? Fertility and Sterility 99 18–22. (https://doi.org/10.1016/j.fertnstert.2012.11.031)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Boucret L, de la Barca JMC, Moriniere C, Desquiret V, Ferre-L’Hotellier V, Descamps P, Marcaillou C, Reynier P, Procaccio V & & May-Panloup P 2015 Relationship between diminished ovarian reserve and mitochondrial biogenesis in cumulus cells. Human Reproduction 30 1653–1664. (https://doi.org/10.1093/humrep/dev114)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Camaioni A, Ucci MA, Campagnolo L, De Felici M, Klinger FG & Italian Society of Embryology, Reproduction and Research (SIERR) 2022 The process of ovarian aging: it is not just about oocytes and granulosa cells. Journal of Assisted Reproduction and Genetics 39 783–792. (https://doi.org/10.1007/s10815-022-02478-0)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chiang JL, Shukla P, Pagidas K, Ahmed NS, Karri S, Gunn DD, Hurd WW & & Singh KK 2020 Mitochondria in ovarian aging and reproductive longevity. Ageing Research Reviews 63 101168. (https://doi.org/10.1016/j.arr.2020.101168)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Desquiret-Dumas V, Clement A, Seegers V, Boucret L, Ferre-L’Hotellier V, Bouet PE, Descamps P, Procaccio V, Reynier P & & May-Panloup P 2017 The mitochondrial DNA content of cumulus granulosa cells is linked to embryo quality. Human Reproduction 32 607–614. (https://doi.org/10.1093/humrep/dew341)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Dumesic DA, Meldrum DR, Katz-Jaffe MG, Krisher RL & & Schoolcraft WB 2015 Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health. Fertility and Sterility 103 303–316. (https://doi.org/10.1016/j.fertnstert.2014.11.015)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Dumesic DA, Guedikian AA, Madrigal VK, Phan JD, Hill DL, Alvarez JP & & Chazenbalk GD 2016 Cumulus cell mitochondrial resistance to stress in vitro predicts oocyte development during assisted reproduction. Journal of Clinical Endocrinology and Metabolism 101 2235–2245. (https://doi.org/10.1210/jc.2016-1464)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Dumoulin B, Heydeck D, Jähn D, Lassé M, Sofi S, Ufer C & & Kuhn H 2022 Male guanine-rich RNA sequence binding factor 1 knockout mice (Grsf1(-/-)) gain less body weight during adolescence and adulthood. Cell and Bioscience 12 199. (https://doi.org/10.1186/s13578-022-00922-3)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Flynn JM & & Melov S 2013 SOD2 in mitochondrial dysfunction and neurodegeneration. Free Radical Biology and Medicine 62 4–12. (https://doi.org/10.1016/j.freeradbiomed.2013.05.027)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gilchrist RB, Lane M & & Thompson JG 2008 Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Human Reproduction Update 14 159–177. (https://doi.org/10.1093/humupd/dmm040)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Jiang L, Huang H, Qian Y, Li Y, Chen X, Di N & & Yang D 2020 miR-130b regulates gap junctional intercellular communication through connexin 43 in granulosa cells from patients with polycystic ovary syndrome. Molecular Human Reproduction 26 576–584. (https://doi.org/10.1093/molehr/gaaa044)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Jourdain AA, Koppen M, Wydro M, Rodley CD, Lightowlers RN, Chrzanowska-Lightowlers ZM & & Martinou JC 2013 GRSF1 regulates RNA processing in mitochondrial RNA granules. Cell Metabolism 17 399–410. (https://doi.org/10.1016/j.cmet.2013.02.005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kerr JB, Myers M & & Anderson RA 2013 The dynamics of the primordial follicle reserve. Reproduction 146 R205–R215. (https://doi.org/10.1530/REP-13-0181)

  • Kim SJ, Chun M, Wan J, Lee C, Yen K & & Cohen P 2019 GRSF1 is an age-related regulator of senescence. Scientific Reports 9 5546. (https://doi.org/10.1038/s41598-019-42064-6)

  • Lan Y, Zhang S, Gong F, Lu C, Lin G & & Hu L 2020 The mitochondrial DNA copy number of cumulus granulosa cells may be related to the maturity of oocyte cytoplasm. Human Reproduction 35 1120–1129. (https://doi.org/10.1093/humrep/deaa085)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lim J & & Luderer U 2011 Oxidative damage increases and antioxidant gene expression decreases with aging in the mouse ovary. Biology of Reproduction 84 775–782. (https://doi.org/10.1095/biolreprod.110.088583)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liu Y, Han M, Li X, Wang H, Ma M, Zhang S, Guo Y, Wang S, Wang Y, Duan N, et al.2017 Age-related changes in the mitochondria of human mural granulosa cells. Human Reproduction 32 2465–2473. (https://doi.org/10.1093/humrep/dex309)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Matos L, Stevenson D, Gomes F, Silva-Carvalho JL & & Almeida H 2009 Superoxide dismutase expression in human cumulus oophorus cells. Molecular Human Reproduction 15 411–419. (https://doi.org/10.1093/molehr/gap034)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • May-Panloup P, Boucret L, Chao de la Barca JM, Desquiret-Dumas V, Ferre-L’Hotellier V, Moriniere C, Descamps P, Procaccio V & & Reynier P 2016 Ovarian ageing: the role of mitochondria in oocytes and follicles. Human Reproduction Update 22 725–743. (https://doi.org/10.1093/humupd/dmw028)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Noh JH, Kim KM, Pandey PR, Noren Hooten N, Munk R, Kundu G, De S, Martindale JL, Yang X, Evans MK, et al.2019 Loss of RNA-binding protein GRSF1 activates mTOR to elicit a proinflammatory transcriptional program. Nucleic Acids Research 47 2472–2486. (https://doi.org/10.1093/nar/gkz082)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ogino M, Tsubamoto H, Sakata K, Oohama N, Hayakawa H, Kojima T, Shigeta M & & Shibahara H 2016 Mitochondrial DNA copy number in cumulus cells is a strong predictor of obtaining good-quality embryos after IVF. Journal of Assisted Reproduction and Genetics 33 367–371. (https://doi.org/10.1007/s10815-015-0621-0)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pan H, Ma P, Zhu W & & Schultz RM 2008 Age-associated increase in aneuploidy and changes in gene expression in mouse eggs. Developmental Biology 316 397–407. (https://doi.org/10.1016/j.ydbio.2008.01.048)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Park SU, Walsh L & & Berkowitz KM 2021 Mechanisms of ovarian aging. Reproduction 162 R19–R33. (https://doi.org/10.1530/REP-21-0022)

  • Pawlak P, Chabowska A, Malyszka N & & Lechniak D 2016 Mitochondria and mitochondrial DNA in porcine oocytes and cumulus cells–A search for developmental competence marker. Mitochondrion 27 48–55. (https://doi.org/10.1016/j.mito.2015.12.008)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Perheentupa A & & Huhtaniemi I 2009 Aging of the human ovary and testis. Molecular and Cellular Endocrinology 299 2–13. (https://doi.org/10.1016/j.mce.2008.11.004)

  • Perkins AT, Greig MM, Sontakke AA, Peloquin AS, McPeek MA & & Bickel SE 2019 Increased levels of superoxide dismutase suppress meiotic segregation errors in aging oocytes. Chromosoma 128 215–222. (https://doi.org/10.1007/s00412-019-00702-y)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pietras Z, Wojcik MA, Borowski LS, Szewczyk M, Kulinski TM, Cysewski D, Stepien PP, Dziembowski A & & Szczesny RJ 2018 Dedicated surveillance mechanism controls G-quadruplex forming non-coding RNAs in human mitochondria. Nature Communications 9 2558. (https://doi.org/10.1038/s41467-018-05007-9)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rehfeldt SCH, Laufer S & & Goettert MI 2021 A highly selective in vitro JNK3 inhibitor, FMU200, restores mitochondrial membrane potential and reduces oxidative stress and apoptosis in SH-SY5Y cells. International Journal of Molecular Sciences 22 3701. (https://doi.org/10.3390/ijms22073701)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sasaki H, Hamatani T, Kamijo S, Iwai M, Kobanawa M, Ogawa S, Miyado K & & Tanaka M 2019 Impact of oxidative stress on age-associated decline in oocyte developmental competence. Frontiers in Endocrinology 10 811. (https://doi.org/10.3389/fendo.2019.00811)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Schofield JH & & Schafer ZT 2021 Mitochondrial reactive oxygen species and mitophagy: a complex and nuanced relationship. Antioxidants and Redox Signaling 34 517–530. (https://doi.org/10.1089/ars.2020.8058)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Seifer DB, DeJesus V & & Hubbard K 2002 Mitochondrial deletions in luteinized granulosa cells as a function of age in women undergoing in vitro fertilization. Fertility and Sterility 78 1046–1048. (https://doi.org/10.1016/s0015-0282(0204214-0)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tatone C, Carbone MC, Falone S, Aimola P, Giardinelli A, Caserta D, Marci R, Pandolfi A, Ragnelli AM & & Amicarelli F 2006 Age-dependent changes in the expression of superoxide dismutases and catalase are associated with ultrastructural modifications in human granulosa cells. Molecular Human Reproduction 12 655–660. (https://doi.org/10.1093/molehr/gal080)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Telfer EE, Grosbois J, Odey YL, Rosario R & & Anderson RA 2023 Making a good egg: human oocyte health, aging, and in vitro development. Physiological Reviews 103 2623–2677. (https://doi.org/10.1152/physrev.00032.2022)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tiwari BS, Belenghi B & & Levine A 2002 Oxidative stress increased respiration and generation of reactive oxygen species, resulting in ATP depletion, opening of mitochondrial permeability transition, and programmed cell death. Plant Physiology 128 1271–1281. (https://doi.org/10.1104/pp.010999)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wang S, Zheng Y, Li J, Yu Y, Zhang W, Song M, Liu Z, Min Z, Hu H, Jing Y, et al.2020 Single-cell transcriptomic atlas of primate ovarian aging. Cell 180 585–600.e19. (https://doi.org/10.1016/j.cell.2020.01.009)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wang L, Tang J, Wang L, Tan F, Song H, Zhou J & & Li F 2021 Oxidative stress in oocyte aging and female reproduction. Journal of Cellular Physiology 236 7966–7983. (https://doi.org/10.1002/jcp.30468)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Xiong X, Lan D, Li J, Lin Y & & Zi X 2018 Effects of zinc supplementation during in vitro maturation on meiotic maturation of oocytes and developmental capacity in yak. Biological Trace Element Research 185 89–97. (https://doi.org/10.1007/s12011-017-1217-6)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhang M, Lu Y, Chen Y, Zhang Y & & Xiong B 2020 Insufficiency of melatonin in follicular fluid is a reversible cause for advanced maternal age-related aneuploidy in oocytes. Redox Biology 28 101327. (https://doi.org/10.1016/j.redox.2019.101327)

    • PubMed
    • Search Google Scholar
    • Export Citation