A mechanism linking perinatal 2,3,7,8 tetrachlorodibenzo-p-dioxin exposure to lower urinary tract dysfunction in adulthood

Anne E. Turco, Steven R. Oakes, Kimberly P.Keil Stietz, Cheryl L. Dunham, Diya B. Joseph, Thrishna S. Chathurvedula, Nicholas M. Girardi, Andrew J. Schneider, Joseph Gawdzik, Celeste M. Sheftel, Peiqing Wang, Zunyi Wang, Dale E. Bjorling, William A. Ricke, Weiping Tang, Laura L. Hernandez, Janet R. Keast, Adrian D. Bonev, Matthew D. Grimes, Douglas W. StrandNathan R. Tykocki, Robyn L. Tanguay, Richard E. Peterson, Chad M. Vezina

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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 ìg/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.

Original languageEnglish (US)
Article numberdmm049068
JournalDMM Disease Models and Mechanisms
Volume14
Issue number7
DOIs
StatePublished - Jul 2021

Keywords

  • Artemin
  • Dioxin
  • Lower urinary tract dysfunction
  • Noradrenergic
  • Prostate
  • Smooth muscle

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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