DYRK1A Overexpression in Mice Downregulates the Gonadotropic Axis and Disturbs Early Stages of Spermatogenesis.
DYRK1A
Down syndrome
infertility
Journal
Genes
ISSN: 2073-4425
Titre abrégé: Genes (Basel)
Pays: Switzerland
ID NLM: 101551097
Informations de publication
Date de publication:
16 11 2021
16 11 2021
Historique:
received:
24
10
2021
revised:
08
11
2021
accepted:
12
11
2021
entrez:
27
11
2021
pubmed:
28
11
2021
medline:
10
2
2022
Statut:
epublish
Résumé
Down syndrome (DS) is the most common chromosomal disorder. It is responsible for intellectual disability (ID) and several medical conditions. Although men with DS are thought to be infertile, some spontaneous paternities have been reported. The few studies of the mechanism of infertility in men with DS are now dated. Recent research in zebrafish has indicated that overexpression of DYRK1A (the protein primarily responsible for ID in DS) impairs gonadogenesis at the embryonic stage. To better ascertain DYRK1A's role in infertility in DS, we investigated the effect of DYRK1A overexpression in a transgenic mouse model. We found that overexpression of DYRK1A impairs fertility in transgenic male mice. Interestingly, the mechanism in mice differs slightly from that observed in zebrafish but, with disruption of the early stages of spermatogenesis, is similar to that seen in humans. Unexpectedly, we observed hypogonadotropic hypogonadism in the transgenic mice.
Identifiants
pubmed: 34828406
pii: genes12111800
doi: 10.3390/genes12111800
pmc: PMC8621272
pii:
doi:
Substances chimiques
Protein-Tyrosine Kinases
EC 2.7.10.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Références
J Clin Invest. 2021 Jan 4;131(1):
pubmed: 33393494
Neuroreport. 2012 Nov 14;23(16):958-62
pubmed: 23032401
Mars Med. 1971;108(1):31-41
pubmed: 4251254
Acta Endocrinol (Copenh). 1978 Jul;88(3):594-600
pubmed: 150188
Physiol Rev. 2016 Jan;96(1):1-17
pubmed: 26537427
Asian J Androl. 2019 Mar-Apr;21(2):109-114
pubmed: 30381580
Horm Res. 1980;12(6):345-50
pubmed: 6448218
Biochem Biophys Res Commun. 2003 Mar 7;302(2):403-8
pubmed: 12604362
PLoS Genet. 2019 May 6;15(5):e1008084
pubmed: 31059511
Biol Reprod. 2010 Sep;83(3):427-33
pubmed: 20505165
Acta Paediatr. 1996 Sep;85(9):1102-6
pubmed: 8888926
Brain Sci. 2018 Oct 16;8(10):
pubmed: 30332747
Neurobiol Dis. 2006 Jun;22(3):463-72
pubmed: 16455265
Cell Mol Life Sci. 2021 Jan;78(2):603-619
pubmed: 32870330
Hum Genet. 1983;63(2):132-8
pubmed: 6220959
Mol Genet Metab. 2013 Nov;110(3):371-7
pubmed: 23920041
Development. 2011 Jul;138(14):2861-9
pubmed: 21693509
Sci Rep. 2017 Nov 10;7(1):15313
pubmed: 29127398
Nucleic Acids Res. 2002 May 1;30(9):e36
pubmed: 11972351
Neurobiol Dis. 2012 Apr;46(1):190-203
pubmed: 22293606
Humangenetik. 1971;13(1):15-24
pubmed: 4256013
Am J Pathol. 1996 May;148(5):1689-98
pubmed: 8623936
J Med Genet. 1982 Apr;19(2):98-9
pubmed: 6210777
Neurobiol Dis. 2014 Sep;69:65-75
pubmed: 24801365
Am J Med Genet. 1987 Jun;27(2):449-58
pubmed: 2955699
Am J Dis Child. 1985 Mar;139(3):236-8
pubmed: 3156491
Am J Ment Defic. 1960 Jul;65:37-41
pubmed: 13833938
Ala J Med Sci. 1966 Apr;3(2):117-20
pubmed: 4223392
Acta Neurol (Napoli). 1975 Jan-Feb;30(1):78-83
pubmed: 131469
J Med Genet. 1989 May;26(5):294-8
pubmed: 2567354
Chromosoma. 1965 Jun 28;16(6):652-7
pubmed: 4222052
Proc Natl Acad Sci U S A. 1970 Sep;67(1):221-4
pubmed: 4248157
Fertil Steril. 2006 Dec;86(6):1765.e1-3
pubmed: 17094988
J Endocr Soc. 2017 Feb 10;1(3):186-201
pubmed: 29264476
Biol Reprod. 2008 Nov;79(5):806-14
pubmed: 18614702
J Pediatr. 2013 Oct;163(4):1163-8
pubmed: 23885965
Mol Reprod Dev. 2020 Apr;87(4):419-429
pubmed: 32020743
Mol Reprod Dev. 2018 Mar;85(3):262-270
pubmed: 29393534
Mol Neurobiol. 2018 May;55(5):3822-3831
pubmed: 28540658
J Clin Endocrinol Metab. 2005 Feb;90(2):724-8
pubmed: 15536161
Eur J Obstet Gynecol Reprod Biol. 2002 Jan 10;100(2):208-12
pubmed: 11750967
Am J Hum Genet. 2007 Sep;81(3):475-91
pubmed: 17701894
Intellect Dev Disabil. 2012 Apr;50(2):155-68
pubmed: 22642969
Fertil Steril. 2002 Apr;77(4):787-93
pubmed: 11937135
Free Radic Biol Med. 2020 Nov 20;160:575-595
pubmed: 32896600
J Cell Mol Med. 2019 Nov;23(11):7427-7437
pubmed: 31454149
Sci Rep. 2020 Sep 15;10(1):15062
pubmed: 32934281
Clin Genet. 1971;2(1):50-7
pubmed: 4255785
Horm Res Paediatr. 2010;73(2):81-92
pubmed: 20190544
Front Physiol. 2017 Mar 29;8:188
pubmed: 28424629