PMID- 32409627
OWN - NLM
STAT- MEDLINE
DCOM- 20210802
LR  - 20231213
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 12
IP  - 10
DP  - 2020 May 14
TI  - Sigma-1 receptor is involved in diminished ovarian reserve possibly by 
      influencing endoplasmic reticulum stress-mediated granulosa cells apoptosis.
PG  - 9041-9065
LID - 10.18632/aging.103166 [doi]
AB  - 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.
FAU - Jiang, Lile
AU  - Jiang L
AD  - Reproductive Medical Center, People's Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
AD  - Department of Obstetrics and Gynecology, The Second Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, Henan, China.
FAU - Cui, Jinquan
AU  - Cui J
AD  - Department of Obstetrics and Gynecology, The Second Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, Henan, China.
FAU - Zhang, Cuilian
AU  - Zhang C
AD  - Reproductive Medical Center, People's Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
FAU - Xie, Juanke
AU  - Xie J
AD  - Reproductive Medical Center, People's Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
FAU - Zhang, Shaodi
AU  - Zhang S
AD  - Reproductive Medical Center, People's Hospital of Zhengzhou University, 
      Zhengzhou, Henan, China.
FAU - Fu, Dongjun
AU  - Fu D
AD  - School of Pharmaceutical Sciences and Collaborative Innovation Center of New Drug 
      Research and Safety Evaluation, Zhengzhou University, Zhengzhou, Henan, China.
FAU - Duo, Wei
AU  - Duo W
AD  - Department of Obstetrics and Gynecology, The Second Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, Henan, China.
LA  - eng
PT  - Journal Article
DEP - 20200514
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (Receptors, sigma)
SB  - IM
MH  - Adult
MH  - *Apoptosis/genetics/physiology
MH  - Endoplasmic Reticulum Stress/*physiology
MH  - Female
MH  - Granulosa Cells/*physiology
MH  - Humans
MH  - Ovarian Reserve/*physiology
MH  - Ovary/cytology/metabolism/pathology
MH  - *Receptors, sigma/genetics/metabolism
MH  - Sigma-1 Receptor
PMC - PMC7288944
OTO - NOTNLM
OT  - apoptosis
OT  - diminished ovarian reserve
OT  - endoplasmic reticulum stress
OT  - granulosa cells
OT  - sigma-1 receptor
COIS- CONFLICTS OF INTEREST: The authors declare that they have no conflicts of 
      interest.
EDAT- 2020/05/16 06:00
MHDA- 2021/08/03 06:00
PMCR- 2020/05/31
CRDT- 2020/05/16 06:00
PHST- 2020/01/07 00:00 [received]
PHST- 2020/03/31 00:00 [accepted]
PHST- 2020/05/16 06:00 [pubmed]
PHST- 2021/08/03 06:00 [medline]
PHST- 2020/05/16 06:00 [entrez]
PHST- 2020/05/31 00:00 [pmc-release]
AID - 103166 [pii]
AID - 10.18632/aging.103166 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2020 May 14;12(10):9041-9065. doi: 10.18632/aging.103166. Epub 
      2020 May 14.