NBMA Promotes Spermatogenesis by Mediating Oct4 Pathway.
NBMA
Oct4
male infertility
spermatogenesis
targeted drug design
Journal
ChemistryOpen
ISSN: 2191-1363
Titre abrégé: ChemistryOpen
Pays: Germany
ID NLM: 101594811
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
26
01
2022
received:
22
09
2021
pubmed:
11
2
2022
medline:
26
4
2022
entrez:
10
2
2022
Statut:
ppublish
Résumé
Non-obstructive azoospermia is one of the most common causes of male infertility, but there is still no specific treatment drug. Given that the Oct4 (Octamer-binding transcription factor 4) has an important regulatory effect on spermatogenesis, activating it can effectively promote spermatogenesis, so it is of great value to develop Oct4-targeted drug design and elucidating its mechanism of action. Here, we screened out the Oct4-targeted drug molecule NBMA (N-benzyl-4-methoxy-2-(1-(4-(trifluoromethyl)phenyl)vinyl)aniline) by computer-assisted technology, and found that it has a significant promoting effect on spermatogenesis in the established mouse azoospermia model. Subsequently, through transcriptome sequencing and enrichment analysis, real-time fluorescent quantitative PCR (qPCR) and western blot experiments revealed that NBMA promotes the differentiation of spermatogonial stem cells by activating the Oct4 pathway, thereby promoting spermatogenesis. This study proves that NBMA is a molecule with great potential to be developed as a therapeutic drug for azoospermia. It also shows that computer-assisted, chemical and biological multidisciplinary methods play a very important role in innovative drug discovery.
Identifiants
pubmed: 35142088
doi: 10.1002/open.202100219
pmc: PMC8889506
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202100219Subventions
Organisme : National Key Research and Development Program of China
ID : 2018YFC1003500
Organisme : Jiangsu Province
ID : 131219631004
Informations de copyright
© 2022 The Authors. Published by Wiley-VCH GmbH.
Références
Stem Cell Reports. 2014 Nov 11;3(5):892-904
pubmed: 25418731
Stem Cells. 2008 Dec;26(12):3068-74
pubmed: 18787205
MMWR Surveill Summ. 2019 Apr 26;68(4):1-23
pubmed: 31022165
Org Lett. 2019 Jan 18;21(2):571-574
pubmed: 30604972
Hum Reprod Update. 2021 Jan 4;27(1):154-189
pubmed: 33118031
Reprod Biol Endocrinol. 2015 Apr 26;13:37
pubmed: 25928197
Dalton Trans. 2019 Apr 2;48(14):4474-4478
pubmed: 30860245
Reprod Med Biol. 2016 Jan 18;15(3):165-173
pubmed: 29259433
Cell Stem Cell. 2010 Apr 2;6(4):382-95
pubmed: 20362542
Nat Genet. 2000 Apr;24(4):372-6
pubmed: 10742100
Cytotechnology. 2018 Apr;70(2):489-495
pubmed: 29159661
Angew Chem Int Ed Engl. 2008;47(27):5056-9
pubmed: 18512215
Stem Cells. 2010 May;28(5):885-93
pubmed: 20333750
Mol Hum Reprod. 2005 Mar;11(3):173-81
pubmed: 15695770
EMBO J. 1990 Jul;9(7):2185-95
pubmed: 2357966
EMBO Rep. 2004 Nov;5(11):1078-83
pubmed: 15486564
Natl Sci Rev. 2019 May;6(3):455-468
pubmed: 31355046
Andrologia. 2017 Sep;49(7):
pubmed: 27921326
J Assist Reprod Genet. 2017 Jan;34(1):149-154
pubmed: 27655389
Chemistry. 2017 Aug 25;23(48):11524-11528
pubmed: 28704583
Cell. 2005 Sep 23;122(6):947-56
pubmed: 16153702
Nucleic Acids Res. 1992 Sep 11;20(17):4613-20
pubmed: 1408763
Curr Biol. 2020 Dec 21;30(24):5007-5017.e4
pubmed: 33065011
J Ovarian Res. 2015 Oct 07;8:66
pubmed: 26446766
Sci Rep. 2016 Dec 12;6:38805
pubmed: 27941834
Nat Cell Biol. 2018 Jun;20(6):655-665
pubmed: 29713018
ChemistryOpen. 2022 Mar;11(3):e202100219
pubmed: 35142088
Elife. 2020 Jul 20;9:
pubmed: 32686646
Stem Cells. 2012 Mar;30(3):441-51
pubmed: 22162380
Hum Reprod. 2015 Jun;30(6):1510-4
pubmed: 25908656