title: In Utero and Lactational TCDD Exposure Increases Susceptibility to Lower Urinary Tract Dysfunction in Adulthood.
abstract: Benign prostatic hyperplasia, prostate cancer, and changes in the ratio of circulating testosterone and estradiol often occur concurrently in aging men and can lead to lower urinary tract (LUT) dysfunction. To explore the possibility of a fetal basis for the development of LUT dysfunction in adulthood, Tg(CMV-cre);Nkx3-1(+/-);Pten(fl/+) mice, which are genetically predisposed to prostate neoplasia, were exposedin uteroand during lactation to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 1 μg/kg po) or corn oil vehicle (5 ml/kg) after a single maternal dose on 13 days post coitus, and subsequently were aged without further manipulation, or at 8 weeks of age were exposed to exogenous 17 β-estradiol (2.5 mg) and testosterone (25 mg) (T+E2) via slow release subcutaneous implants.In uteroand lactational (IUL) TCDD exposure in the absence of exogenous hormone treatment reduced voiding pressure in adult mice, but otherwise had little effect on mouse LUT anatomy or function. By comparison, IUL TCDD exposure followed by exogenous hormone treatment increased relative kidney, bladder, dorsolateral prostate, and seminal vesicle weights, hydronephrosis incidence, and prostate epithelial cell proliferation, thickened prostate periductal smooth muscle, and altered prostate and bladder collagen fiber distribution. We propose a 2-hit model whereby IUL TCDD exposure sensitizes mice to exogenous-hormone-induced urinary tract dysfunction later in life.
authors: *Molecular and Environmental Toxicology Center; Department of Urology; University of Wisconsin Carbone Cancer Center; George M. O'Brien Benign Urology Center of Research Excellence;
authors: William A
authors: WA
authors: Ricke
authors: School of Pharmacy; and.
authors: Calvin W
authors: CW
authors: Lee
authors: School of Pharmacy; and.
authors: Tyler R
authors: TR
authors: Clapper
authors: School of Pharmacy; and.
authors: Andrew J
authors: AJ
authors: Schneider
authors: School of Pharmacy; and.
authors: Robert W
authors: RW
authors: Moore
authors: School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706.
authors: Kimberly P
authors: KP
authors: Keil
authors: School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706.
authors: Lisa L
authors: LL
authors: Abler
authors: *Molecular and Environmental Toxicology Center;
authors: Jalissa L
authors: JL
authors: Wynder
authors: *Molecular and Environmental Toxicology Center;
authors: Arnaldo
authors: A
authors: López Alvarado
authors: *Molecular and Environmental Toxicology Center;
authors: Isaac
authors: I
authors: Beaubrun
authors: *Molecular and Environmental Toxicology Center;
authors: Jenny
authors: J
authors: Vo
authors: Department of Urology;
authors: Tyler M
authors: TM
authors: Bauman
authors: Department of Urology;
authors: Emily A
authors: EA
authors: Ricke
authors: *Molecular and Environmental Toxicology Center; University of Wisconsin Carbone Cancer Center; School of Pharmacy; and.
authors: Richard E
authors: RE
authors: Peterson
authors: *Molecular and Environmental Toxicology Center; Department of Urology; University of Wisconsin Carbone Cancer Center; George M. O'Brien Benign Urology Center of Research Excellence; School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706 cmvezina@wisc.edu.
authors: Chad M
authors: CM
authors: Vezina
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D020022:Genetic Predisposition to Disease; D007774:Lactation / Q000378:metabolism; D059411:Lower Urinary Tract Symptoms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000493:pharmacokinetics / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011467:Prostate / Q000187:drug effects / Q000196:embryology; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D012669:Seminal Vesicles / Q000187:drug effects / Q000196:embryology; D013739:Testosterone / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000196:embryology
chemical_list: D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D013739:Testosterone; D004997:Ethinyl Estradiol
keywords: Lower urinary tract symptoms (LUTS); TCDD; fetal basis of adult disease; hydronephrosis.; mouse; prostate