Could perturbed fetal development of the ovary contribute to the development of polycystic ovary syndrome in later life?
Adult
Animals
Biomarkers
/ analysis
Cattle
Female
Fetal Development
/ genetics
Gene Expression Regulation, Developmental
Genes, Regulator
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Ovary
/ metabolism
Polycystic Ovary Syndrome
/ genetics
Polymorphism, Single Nucleotide
Pregnancy
Stromal Cells
/ metabolism
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
27
11
2019
accepted:
04
02
2020
entrez:
21
2
2020
pubmed:
23
2
2020
medline:
10
5
2020
Statut:
epublish
Résumé
Polycystic ovary syndrome (PCOS) affects around 10% of young women, with adverse consequences on fertility and cardiometabolic outcomes. PCOS appears to result from a genetic predisposition interacting with developmental events during fetal or perinatal life. We hypothesised that PCOS candidate genes might be expressed in the fetal ovary when the stroma develops; mechanistically linking the genetics, fetal origins and adult ovarian phenotype of PCOS. In bovine fetal ovaries (n = 37) of 18 PCOS candidate genes only SUMO1P1 was not expressed. Three patterns of expression were observed: early gestation (FBN3, GATA4, HMGA2, TOX3, DENND1A, LHCGR and FSHB), late gestation (INSR, FSHR, and LHCGR) and throughout gestation (THADA, ERBB4, RAD50, C8H9orf3, YAP1, RAB5B, SUOX and KRR1). A splice variant of FSHB exon 3 was also detected early in the bovine ovaries, but exon 2 was not detected. Three other genes, likely to be related to the PCOS aetiology (AMH, AR and TGFB1I1), were also expressed late in gestation. Significantly within each of the three gene groups, the mRNA levels of many genes were highly correlated with each other, despite, in some instances, being expressed in different cell types. TGFβ is a well-known stimulator of stromal cell replication and collagen synthesis and TGFβ treatment of cultured fetal ovarian stromal cells inhibited the expression of INSR, AR, C8H9orf3 and RAD50 and stimulated the expression of TGFB1I1. In human ovaries (n = 15, < 150 days gestation) many of the same genes as in bovine (FBN3, GATA4, HMGA2, FSHR, DENND1A and LHCGR but not TOX3 or FSHB) were expressed and correlated with each other. With so many relationships between PCOS candidate genes during development of the fetal ovary, including TGFβ and androgen signalling, we suggest that future studies should determine if perturbations of these genes in the fetal ovary can lead to PCOS in later life.
Identifiants
pubmed: 32078641
doi: 10.1371/journal.pone.0229351
pii: PONE-D-19-32933
pmc: PMC7032716
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0229351Subventions
Organisme : Medical Research Council
ID : MR/N022556/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1100357
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Fertil Steril. 2016 Jul;106(1):25-32
pubmed: 27179787
J Clin Endocrinol Metab. 2009 Nov;94(11):4361-6
pubmed: 19837913
Obstet Gynecol Surv. 1982 Feb;37(2):59-77
pubmed: 7033852
J Psychiatr Res. 2012 Feb;46(2):271-8
pubmed: 22126837
Hum Reprod Update. 2017 Jul 1;23(4):421-432
pubmed: 28531286
J Steroid Biochem Mol Biol. 2015 Jan;145:213-25
pubmed: 25008465
Nat Genet. 2011 Jan;43(1):55-9
pubmed: 21151128
Lancet. 2007 Aug 25;370(9588):685-97
pubmed: 17720020
Best Pract Res Clin Endocrinol Metab. 2018 Jun;32(3):271-281
pubmed: 29779581
Mol Cell Endocrinol. 2010 Jun 10;321(2):207-14
pubmed: 20176077
J Cell Sci. 2010 Sep 1;123(Pt 17):3006-18
pubmed: 20699357
Dev Biol. 2008 Feb 1;314(1):189-99
pubmed: 18166170
Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
pubmed: 12184808
BMC Med. 2010 Jun 30;8:41
pubmed: 20591140
Anal Biochem. 2011 Sep 1;416(1):123-5
pubmed: 21624343
Methods Mol Biol. 2000;132:365-86
pubmed: 10547847
Curr Opin Endocrinol Diabetes Obes. 2016 Jun;23(3):257-63
pubmed: 26866639
Reprod Biomed Online. 2016 Jun;32(6):635-41
pubmed: 27061682
Reproduction. 2016 Aug;152(2):127-37
pubmed: 27222596
Int J Gynaecol Obstet. 1989 May;29(1):35-8
pubmed: 2566526
J Mol Biol. 2000 Sep 8;302(1):205-17
pubmed: 10964570
Steroids. 2013 Aug;78(8):734-40
pubmed: 23701728
Nat Med. 2018 Jun;24(6):834-846
pubmed: 29760445
Iran J Reprod Med. 2014 Jul;12(7):499-506
pubmed: 25114673
FASEB J. 2011 Jul;25(7):2256-65
pubmed: 21411746
J Assist Reprod Genet. 2014 Mar;31(3):371-7
pubmed: 24390680
J Clin Endocrinol Metab. 2019 Nov 1;104(11):5372-5381
pubmed: 30938770
Hum Reprod. 2017 May 1;32(5):1075-1091
pubmed: 28333286
Nat Rev Dis Primers. 2016 Aug 11;2:16057
pubmed: 27510637
Nat Genet. 2012 Sep;44(9):1020-5
pubmed: 22885925
PLoS One. 2019 Mar 11;14(3):e0213575
pubmed: 30856218
Proc Natl Acad Sci U S A. 2014 Apr 15;111(15):E1519-27
pubmed: 24706793
PLoS One. 2019 Mar 22;14(3):e0214130
pubmed: 30901367
J Clin Endocrinol Metab. 2007 Nov;92(11):4191-8
pubmed: 17785364
Nat Commun. 2015 Sep 29;6:8464
pubmed: 26416764
Respirology. 2018 Dec;23(12):1096-1097
pubmed: 30284753
Med Hypotheses. 2019 Mar;124:31-34
pubmed: 30798911
Trends Endocrinol Metab. 2015 Mar;26(3):118-24
pubmed: 25600292
Reprod Fertil Dev. 2019 Mar;31(3):482-495
pubmed: 30501845
Bibl Anat. 1983;24:77-92
pubmed: 6847603
Theriogenology. 2008 Jan 1;69(1):72-80
pubmed: 17980420
Reprod Sci. 2014 Jan;21(1):20-31
pubmed: 23585338
J Anat. 1986 Oct;148:121-35
pubmed: 3693081
Endocrine. 2006 Aug;30(1):19-26
pubmed: 17185788
Rev Endocr Metab Disord. 2007 Jun;8(2):127-41
pubmed: 17659447
PLoS One. 2013;8(2):e55578
pubmed: 23409002
Med J Aust. 2011 Sep 19;195(6):S65-112
pubmed: 21929505
J Clin Endocrinol Metab. 2006 Jun;91(6):2100-4
pubmed: 16219714
Hum Reprod. 2010 Feb;25(2):544-51
pubmed: 19910321
Endocr Connect. 2019 Mar;8(3):R71-R75
pubmed: 30763275
J Clin Endocrinol Metab. 2009 Jun;94(6):1883-5
pubmed: 19494163
Hum Reprod. 2012 May;27(5):1475-80
pubmed: 22373955
Nat Commun. 2015 Aug 18;6:7502
pubmed: 26284813
Nature. 2009 Oct 8;461(7265):747-53
pubmed: 19812666
J Biol Chem. 2011 Apr 22;286(16):13791-800
pubmed: 21330364
BMC Dev Biol. 2015 Jan 21;15:4
pubmed: 25605128
Mol Cell Endocrinol. 2002 May 31;191(1):1-10
pubmed: 12044912
Hum Reprod. 2016 Dec;31(12):2841-2855
pubmed: 27664216
Sex Dev. 2009;3(6):291-301
pubmed: 20130386
Eur Rev Med Pharmacol Sci. 2017 May;21(9):2034-2038
pubmed: 28537684
J Clin Endocrinol Metab. 2015 Dec;100(12):E1560-7
pubmed: 26431507
Neurosci Lett. 2003 Mar 13;339(1):62-6
pubmed: 12618301
Mol Cell Endocrinol. 2016 Oct 15;434:25-35
pubmed: 27297658