Single-Oocyte Gene Expression Suggests That Curcumin Can Protect the Ovarian Reserve by Regulating the PTEN-AKT-FOXO3a Pathway.
Animals
Cells, Cultured
Curcumin
/ pharmacology
Female
Forkhead Box Protein O3
/ metabolism
Mice
Mice, Inbred C57BL
Oocytes
/ cytology
Oogenesis
Ovarian Follicle
/ cytology
Ovarian Reserve
PTEN Phosphohydrolase
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Signal Transduction
Single-Cell Analysis
Transcriptome
curcumin
follicle activation
ingenuity pathway analysis
ovarian reserve
primordial follicle
single cell qPCR
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
18 Jun 2021
18 Jun 2021
Historique:
received:
24
05
2021
revised:
11
06
2021
accepted:
14
06
2021
entrez:
2
7
2021
pubmed:
3
7
2021
medline:
14
7
2021
Statut:
epublish
Résumé
A better understanding of the mechanism of primordial follicle activation will help us better understand the causes of premature ovarian insufficiency (POI), and will help us identify new drugs that can be applied to the clinical treatment of infertility. In this study, single oocytes were isolated from primordial and primary follicles, and were used for gene profiling with TaqMan array cards. Bioinformatics analysis was performed on the gene expression data, and Ingenuity Pathway Analysis was used to analyze and predict drugs that affect follicle activation. An ovarian in vitro culture system was used to verify the function of the drug candidates, and we found that curcumin maintains the ovarian reserve. Long-term treatment with 100 mg/kg curcumin improved the ovarian reserve indicators of AMH, FSH, and estradiol in aging mice. Mechanistic studies show that curcumin can affect the translocation of FOXO3, thereby inhibiting the PTEN-AKT-FOXO3a pathway and protecting primordial follicles from overactivation. These results suggest that curcumin is a potential drug for the treatment of POI patients and for fertility preservation.
Identifiants
pubmed: 34207376
pii: ijms22126570
doi: 10.3390/ijms22126570
pmc: PMC8235657
pii:
doi:
Substances chimiques
Forkhead Box Protein O3
0
FoxO3 protein, mouse
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
PTEN Phosphohydrolase
EC 3.1.3.67
Pten protein, mouse
EC 3.1.3.67
Curcumin
IT942ZTH98
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Key Research and Development Program of China
ID : 2017YFC1001000
Références
J Pineal Res. 2016 Apr;60(3):336-47
pubmed: 26882203
Int J Mol Sci. 2019 Feb 27;20(5):
pubmed: 30818786
Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10280-4
pubmed: 20479243
Reprod Biomed Online. 2017 Jan;34(1):104-114
pubmed: 27815062
Mol Reprod Dev. 2013 Jan;80(1):70-8
pubmed: 23212987
Endocr Regul. 2017 Oct 26;51(4):220-228
pubmed: 29232190
J Ovarian Res. 2018 Apr 26;11(1):33
pubmed: 29699594
J Transl Med. 2019 Nov 14;17(1):372
pubmed: 31727091
J Physiol. 2017 Sep 1;595(17):5765-5780
pubmed: 28605113
BMC Biol. 2018 Jul 5;16(1):73
pubmed: 29976179
Lancet Glob Health. 2020 Feb;8(2):e204-e214
pubmed: 31864916
Food Funct. 2018 Feb 21;9(2):705-714
pubmed: 29206254
Reproduction. 2009 Jan;137(1):1-11
pubmed: 18827065
Mol Cell. 2018 Dec 20;72(6):1021-1034.e4
pubmed: 30472193
Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17474-9
pubmed: 24082083
Animal. 2018 Jun;12(6):1242-1249
pubmed: 29070088
Neuroscience. 2019 May 15;406:1-21
pubmed: 30825584
Cells. 2020 Jan 14;9(1):
pubmed: 31947601
J Clin Endocrinol Metab. 2011 Dec;96(12):3864-72
pubmed: 21994953
Cell Cycle. 2013 Oct 15;12(20):3245-6
pubmed: 24036538
Arch Toxicol. 2017 Apr;91(4):1623-1634
pubmed: 28204864
BMC Biol. 2015 Jun 16;13:39
pubmed: 26076587
Mol Hum Reprod. 2009 Dec;15(12):765-70
pubmed: 19843635
Foods. 2017 Oct 22;6(10):
pubmed: 29065496
Anim Reprod Sci. 2012 Apr;131(3-4):129-34
pubmed: 22516229
Anticancer Res. 2003 Jan-Feb;23(1A):363-98
pubmed: 12680238
Cell Cycle. 2015;14(5):721-31
pubmed: 25590233
J Mol Endocrinol. 2018 Apr;60(3):261-271
pubmed: 29437881
Clin Cancer Res. 2007 Jun 1;13(11):3423-30
pubmed: 17545551
Sci Transl Med. 2013 May 15;5(185):185ra62
pubmed: 23677591
Bioinformatics. 2014 Feb 15;30(4):523-30
pubmed: 24336805
Int J Surg. 2013;11(9):967-70
pubmed: 23796447
Fertil Steril. 2015 Mar;103(3):e9-e17
pubmed: 25585505
Proc Natl Acad Sci U S A. 2021 Jan 12;118(2):
pubmed: 33397719
Hum Reprod Update. 2005 Jul-Aug;11(4):391-410
pubmed: 15919682
Endocr Rev. 2000 Apr;21(2):200-14
pubmed: 10782364
Biomed Rep. 2015 Nov;3(6):807-813
pubmed: 26623020
Fertil Steril. 1995 Aug;64(2):273-8
pubmed: 7615102
Mol Cell Endocrinol. 2002 Jun 28;192(1-2):37-43
pubmed: 12088865
Proc Natl Acad Sci U S A. 2016 Aug 9;113(32):9021-6
pubmed: 27457928
Sci Rep. 2017 Jul 31;7(1):6961
pubmed: 28761164
Science. 2008 Feb 1;319(5863):611-3
pubmed: 18239123
Reproduction. 2014 Jun;147(6):865-74
pubmed: 24614542
BMC Genomics. 2013 Dec 19;14:904
pubmed: 24350644
Obstet Gynecol. 1986 Apr;67(4):604-6
pubmed: 3960433
Molecules. 2016 Feb 25;21(3):264
pubmed: 26927041
ACS Nano. 2021 Feb 23;15(2):2812-2830
pubmed: 33527830
Int J Dev Biol. 2012;56(10-12):809-17
pubmed: 23417403
Mol Cell Endocrinol. 2001 Apr 25;175(1-2):123-30
pubmed: 11325522
Hum Reprod Update. 1999 Sep-Oct;5(5):483-92
pubmed: 10582785
Dev Biol. 2008 Sep 1;321(1):197-204
pubmed: 18601916
Endocr Rev. 2021 Apr 14;:
pubmed: 33851994
Trends Endocrinol Metab. 2010 Feb;21(2):96-103
pubmed: 19913438