A mechanism linking perinatal 2,3,7,8 tetrachlorodibenzo-p-dioxin exposure to lower urinary tract dysfunction in adulthood.
Artemin
Dioxin
Lower urinary tract dysfunction
Noradrenergic
Prostate
Smooth muscle
Journal
Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332
Informations de publication
Date de publication:
01 07 2021
01 07 2021
Historique:
received:
15
04
2021
accepted:
15
06
2021
entrez:
28
7
2021
pubmed:
29
7
2021
medline:
1
4
2022
Statut:
ppublish
Résumé
Benign prostatic hyperplasia/lower urinary tract dysfunction (LUTD) affects nearly all men. Symptoms typically present in the fifth or sixth decade and progressively worsen over the remainder of life. Here, we identify a surprising origin of this disease that traces back to the intrauterine environment of the developing male, challenging paradigms about when this disease process begins. We delivered a single dose of a widespread environmental contaminant present in the serum of most Americans [2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), 1 µg/kg], and representative of a broader class of environmental contaminants, to pregnant mice and observed an increase in the abundance of a neurotrophic factor, artemin, in the developing mouse prostate. Artemin is required for noradrenergic axon recruitment across multiple tissues, and TCDD rapidly increases prostatic noradrenergic axon density in the male fetus. The hyperinnervation persists into adulthood, when it is coupled to autonomic hyperactivity of prostatic smooth muscle and abnormal urinary function, including increased urinary frequency. We offer new evidence that prostate neuroanatomical development is malleable and that intrauterine chemical exposures can permanently reprogram prostate neuromuscular function to cause male LUTD in adulthood.
Identifiants
pubmed: 34318329
pii: 271057
doi: 10.1242/dmm.049068
pmc: PMC8326766
pii:
doi:
Substances chimiques
Polychlorinated Dibenzodioxins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : K12 DK100022
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK103840
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES001332
Pays : United States
Organisme : NIEHS NIH HHS
ID : F31 ES030968
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD094759
Pays : United States
Organisme : NIMHD NIH HHS
ID : U01 HD094759
Pays : United States
Organisme : NIEHS NIH HHS
ID : R00 ES029537
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES007015
Pays : United States
Organisme : NIDDK NIH HHS
ID : U54 DK104310
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK119615
Pays : United States
Informations de copyright
© 2021. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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