Sigma-1 Receptor is Involved in Diminished Ovarian Reserve Possibly by Influencing Endoplasmic Reticulum Stress-mediated Granulosa Cells Apoptosis

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2020 May 16

PMID 32409627

Citations 3

Authors

Lile Jiang

Jinquan Cui

Cuilian Zhang

Juanke Xie

Shaodi Zhang

Dongjun Fu

Wei Duo

Affiliations

Soon will be listed here.

Abstract

Sigma non-opioid intracellular receptor 1 (sigma-1 receptor), a non-opioid transmembrane protein, is located on cellular mitochondrial membranes and endoplasmic reticulum. Current research has demonstrated that sigma-1 receptor is related to human degenerative diseases. This study is focused on the effects of sigma-1 receptor on the pathophysiological process of diminished ovarian reserve (DOR) and granulosa cells (GCs) apoptosis. Sigma-1 receptor concentration in follicular fluid (FF) and serum were negatively correlated with basal follicle-stimulating hormone (FSH) and positively correlated with anti-mullerian hormone (AMH), antral follicle count (AFC). Sigma-1 receptor reduction in GCs was accompanied by endoplasmic reticulum stress (ERS)-mediated apoptosis in women with DOR. Plasmid transfection was used to establish SIGMAR1-overexpressed and SIGMAR1-knockdown human granulosa-like tumor (KGN) cell and thapsigargin (TG) was used to induce ERS KGN cells. We found that KGN cells treated with endogenous sigma-1 receptor ligand dehydroepiandrosterone (DHEA) and sigma-1 receptor agonist PRE-084 showed similar biological effects to SIGMAR1-overexpressed KGN cells and opposite effects to SIGMAR1-knockdown KGN cells. DHEA may improve DOR patients' pregnancy outcomes by upregulating sigma-1 receptor and downregulating ERS-mediated apoptotic genes in GCs. Thus, sigma-1 receptor may be a potential ovarian reserve biomarker, and ligand-mediated sigma-1 receptor activation could be a future approach for DOR therapy.

Citing Articles

Facilitation of Ovarian Response by Mechanical Force-Latest Insight on Fertility Improvement in Women with Poor Ovarian Response or Primary Ovarian Insufficiency.

Chang C Int J Mol Sci. 2023; 24(19).

PMID: 37834198 PMC: 10573075. DOI: 10.3390/ijms241914751.

Intracellular dynamics of the Sigma-1 receptor observed with super-resolution imaging microscopy.

Kopanchuk S, Vavers E, Veiksina S, Ligi K, Zvejniece L, Dambrova M PLoS One. 2022; 17(5):e0268563.

PMID: 35584184 PMC: 9116656. DOI: 10.1371/journal.pone.0268563.

Expression of pro-apoptotic and anti-apoptotic proteins in granulosa cells of women with diminished ovarian reserve.

Bulgurcuoglu Kuran S, Altun A, Balci B, Keskin I, Hocaoglu M J Assist Reprod Genet. 2022; 39(3):765-775.

PMID: 35142968 PMC: 8995233. DOI: 10.1007/s10815-022-02422-2.

References

Zheng H, Chen S, Du H, Ling J, Wu Y, Liu H . Ovarian response prediction in controlled ovarian stimulation for IVF using anti-Müllerian hormone in Chinese women: A retrospective cohort study. Medicine (Baltimore). 2017; 96(13):e6495. PMC: 5380281. DOI: 10.1097/MD.0000000000006495. View

Nishi Y, Yanase T, Mu Y, Oba K, Ichino I, Saito M . Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor. Endocrinology. 2001; 142(1):437-45. DOI: 10.1210/endo.142.1.7862. View

Yang D, Jiang T, Lin P, Chen H, Wang L, Wang N . Knock-down of apoptosis inducing factor gene protects endoplasmic reticulum stress-mediated goat granulosa cell apoptosis. Theriogenology. 2016; 88:89-97. DOI: 10.1016/j.theriogenology.2016.10.001. View

Yun B, Kim G, Park S, Noe E, Seo S, Cho S . fertilization outcome in women with diminished ovarian reserve. Obstet Gynecol Sci. 2017; 60(1):46-52. PMC: 5313363. DOI: 10.5468/ogs.2017.60.1.46. View

Li Z, Zhou R, Cui S, Xie G, Cai W, Sokabe M . Dehydroepiandrosterone sulfate prevents ischemia-induced impairment of long-term potentiation in rat hippocampal CA1 by up-regulating tyrosine phosphorylation of NMDA receptor. Neuropharmacology. 2006; 51(5):958-66. DOI: 10.1016/j.neuropharm.2006.06.007. View

Zhang Y, Shi Y, Qiao L, Sun Y, Ding W, Zhang H . Sigma-1 receptor agonists provide neuroprotection against gp120 via a change in bcl-2 expression in mouse neuronal cultures. Brain Res. 2011; 1431:13-22. DOI: 10.1016/j.brainres.2011.10.053. View

Su T, London E, Jaffe J . Steroid binding at sigma receptors suggests a link between endocrine, nervous, and immune systems. Science. 1988; 240(4849):219-21. DOI: 10.1126/science.2832949. View

Manabe N, Goto Y, Matsuda-Minehata F, Inoue N, Maeda A, Sakamaki K . Regulation mechanism of selective atresia in porcine follicles: regulation of granulosa cell apoptosis during atresia. J Reprod Dev. 2004; 50(5):493-514. DOI: 10.1262/jrd.50.493. View

Narkwichean A, Maalouf W, Baumgarten M, Polanski L, Raine-Fenning N, Campbell B . Efficacy of Dehydroepiandrosterone (DHEA) to overcome the effect of ovarian ageing (DITTO): A proof of principle double blinded randomized placebo controlled trial. Eur J Obstet Gynecol Reprod Biol. 2017; 218:39-48. DOI: 10.1016/j.ejogrb.2017.09.006. View

10.

Charalampopoulos I, Alexaki V, Lazaridis I, Dermitzaki E, Avlonitis N, Tsatsanis C . G protein-associated, specific membrane binding sites mediate the neuroprotective effect of dehydroepiandrosterone. FASEB J. 2006; 20(3):577-9. DOI: 10.1096/fj.05-5078fje. View

11.

Garavaglia E, Sala C, Taccagni G, Traglia M, Barbieri C, Ferrari S . Fertility Preservation in Endometriosis Patients: Anti-Müllerian Hormone Is a Reliable Marker of the Ovarian Follicle Density. Front Surg. 2017; 4:40. PMC: 5524724. DOI: 10.3389/fsurg.2017.00040. View

12.

Gundlach A, Largent B, Snyder S . Autoradiographic localization of sigma receptor binding sites in guinea pig and rat central nervous system with (+)3H-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine. J Neurosci. 1986; 6(6):1757-70. PMC: 6568729. View

13.

Tal R, Seifer D . Ovarian reserve testing: a user's guide. Am J Obstet Gynecol. 2017; 217(2):129-140. DOI: 10.1016/j.ajog.2017.02.027. View

14.

Greene A, Patounakis G, Segars J . Genetic associations with diminished ovarian reserve: a systematic review of the literature. J Assist Reprod Genet. 2014; 31(8):935-46. PMC: 4130940. DOI: 10.1007/s10815-014-0257-5. View

15.

Sai T, Goto Y, Yoshioka R, Maeda A, Matsuda F, Sugimoto M . Bid and Bax are involved in granulosa cell apoptosis during follicular atresia in porcine ovaries. J Reprod Dev. 2011; 57(3):421-7. DOI: 10.1262/jrd.11-007h. View

16.

Qin J, Fan L, Qin A . The effect of dehydroepiandrosterone (DHEA) supplementation on women with diminished ovarian reserve (DOR) in IVF cycle: Evidence from a meta-analysis. J Gynecol Obstet Hum Reprod. 2017; 46(1):1-7. DOI: 10.1016/j.jgyn.2016.01.002. View

17.

Hayashi T, Hayashi E, Fujimoto M, Sprong H, Su T . The lifetime of UDP-galactose:ceramide galactosyltransferase is controlled by a distinct endoplasmic reticulum-associated degradation (ERAD) regulated by sigma-1 receptor chaperones. J Biol Chem. 2012; 287(51):43156-69. PMC: 3522309. DOI: 10.1074/jbc.M112.380444. View

18.

Pal L, Santoro N . Age-related decline in fertility. Endocrinol Metab Clin North Am. 2003; 32(3):669-88. DOI: 10.1016/s0889-8529(03)00046-x. View

19.

Rao R, Poksay K, Castro-Obregon S, Schilling B, Row R, Del Rio G . Molecular components of a cell death pathway activated by endoplasmic reticulum stress. J Biol Chem. 2003; 279(1):177-87. DOI: 10.1074/jbc.M304490200. View

20.

Fouany M, Sharara F . Is there a role for DHEA supplementation in women with diminished ovarian reserve?. J Assist Reprod Genet. 2013; 30(9):1239-44. PMC: 3800538. DOI: 10.1007/s10815-013-0018-x. View