Impact of a folic acid-enriched diet on urinary tract function in mice treated with testosterone and estradiol

Keil, Kimberly P.; Abler, Lisa L.; Altmann, Helene M.; Wang, Zunyi; Wang, Peiqing; Ricke, William A.; Bjorling, Dale E.; Vezina, Chad M.

doi:10.1152/ajprenal.00674.2014

Cited by 16 publications

(18 citation statements)

References 37 publications

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“…Male offspring were aged to 8 weeks old (early adulthood) and a subset were implanted subcutaneously with compressed pellets of testosterone (T, 25 mg, Steraloids, Newport, Rhode Island) and 17 bÀestradiol (E 2 , 2.5 mg and cholesterol, 22.5 mg, Sigma Aldrich, St. Louis, Missouri). The testosterone and 17 bÀestradiol doses were selected to match reference studies and because they are sufficient to cause urinary dysfunction in C57BL/6J mice (Keil et al, 2015;Nicholson et al, 2015Nicholson et al, , 2012. Mice were maintained after surgery for up to 4.1 months but euthanized earlier if moribund or recommended for euthanasia by the veterinarian.…”

Section: Micementioning

confidence: 99%

“…Void spot assays (VSAs) were conducted and analyzed as described previously (Bjorling et al, 2015;Keil et al, 2015;Nicholson et al, 2015;Yu et al, 2014). Mice were removed from their cages and singly housed in a clean, empty cage lined with 3 MM Whatman filter paper (Fisher Scientific No.057163W).…”

Section: Spontaneous Void Spot Assaymentioning

confidence: 99%

“…There is considerable variation in age of onset, progression, and severity of LUTS and the underlying basis for this variation is likely multifactorial. Recent studies in mice show that urinary function varies considerably across strains (Tam et al, 2015;Yu et al, 2014), genetic risk factors are strongly implicated in early onset or severe LUTS (Doehring et al, 1996;Partin et al, 1994;Pearson et al, 2003;Sanda et al, 1994), and dietary factors are also likely to play a role (Keil et al, 2015). Geneenvironment interactions are implicated in many diseases, yet few studies have addressed whether environmental chemicals influence baseline urinary function, age of LUTS onset or severity.…”

mentioning

confidence: 99%

“…In this study, we test the hypothesis that in utero and lactational (IUL) TCDD exposure exacerbates urinary dysfunction in adult mice. Because BPH/LUTS and prostate cancer often coexist in men (Bostwick et al, 1992;Ornstein et al, 1997;Sheldon et al, 1980), and because the ratio of circulating sex steroids changes as men age (Belanger et al, 1994), we recapitulated aspects of this complex environment by using a mouse strain susceptible to prostate neoplasia (Tg[CMV-cre];Nkx3-1 þ/À ;Pten fl/þ ) (Abate-Shen et al, 2003) and by exposing mice in adulthood to exogenous testosterone and 17 b-estradiol (T þ E 2 ), which disrupt urinary function (Bernoulli et al, 2008;Keil et al, 2015;Nicholson et al, 2012Nicholson et al, , 2015Noble, 1977;Ricke et al, 2006Ricke et al, , 2008. Our results indicate that IUL TCDD exposure increases the severity of adult urinary dysfunction in TCDD and T þ E 2 -treated mice, providing some of the first evidence that exposure to an environmental contaminant during a male's fetal and neonatal development may adversely impact lifelong urinary health.…”

mentioning

confidence: 99%

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In Uteroand Lactational TCDD Exposure Increases Susceptibility to Lower Urinary Tract Dysfunction in Adulthood

Ricke

Lee²,

Clapper³

et al. 2016

Toxicol. Sci.

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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.

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Section: Micementioning

confidence: 99%

Section: Spontaneous Void Spot Assaymentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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In Uteroand Lactational TCDD Exposure Increases Susceptibility to Lower Urinary Tract Dysfunction in Adulthood

Ricke

Lee²,

Clapper³

et al. 2016

Toxicol. Sci.

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“…Folates are also involved in the synthesis of polyamines, depletion of which has been proposed as a prostate cancer therapy . We reported previously that a FA enriched diet given from conception through adulthood diminishes urinary symptom severity in male mice with hormone induced urinary obstruction . However, the impact of folic acid supplementation on adult prostate homeostasis has not been specifically investigated.…”

Section: Introductionmentioning

confidence: 99%

A folic acid‐enriched diet attenuates prostate involution in response to androgen deprivation

et al. 2018

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Background Serum folate concentrations in the United States have risen since dietary folic acid fortification was first mandated in 1998. Although maternal folic acid offers protection against neural tube defects in conceptuses, its impact on other organ systems and life stages have not been fully examined. Here, we used a mouse model to investigate the impact of a Folic acid (FA) enriched diet on prostate homeostasis and response to androgen deprivation. Methods Male mice were fed a control diet (4 mg FA/kg feed) or a folic acid supplemented diet (24 mg FA/kg feed) beginning at conception and continuing through early adulthood, when mice were castrated. Results We made the surprising observation that dietary FA supplementation confers partial resistance to castration‐mediated prostate involution. At 3, 10, and 14 days post‐castration, FA enriched diet fed mice had larger prostates as assessed by wet weight, taller prostatic luminal epithelial cells, and more abundant RNAs encoding prostate secretory proteins than castrated control diet fed mice. Diet did not significantly affect prostate weights of intact mice or serum testosterone concentrations of castrated mice. RNA‐Seq analysis revealed that the FA enriched diet was associated with a unique prostate gene expression signature, affecting several signaling and metabolic pathways. Conclusions Continuous exposure to a FA enriched diet slows prostate involution in response to androgen deprivation. Prostates from FA diet mice have increased secretory gene expression and increased luminal cell heights. The influence of dietary FA supplementation on the prostate response to androgen deprivation raises a future need to consider how dietary folic acid supplementation affects efficacy of androgen‐reducing therapies for treating prostate disease.

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Potential therapeutic value of transient receptor potential channels in male urogenital system

Toktanis¹,

Kaya‐Sezginer

Yilmaz‐Oral

et al. 2018

Pflugers Arch - Eur J Physiol

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Transient receptor potential (TRP) channels comprise a family of cation channels implicated in a variety of cellular processes including light, mechanical or chemical stimuli, temperature, pH, or osmolarity. TRP channel proteins are a diverse family of proteins that are expressed in many tissues. We debated our recent knowledge about the expression, function, and regulation of TRP channels in the different parts of the male urogenital system in health and disease. Emerging evidence suggests that dysfunction of TRP channels significantly contributes to the pathophysiology of urogenital diseases. So far, there are many efforts underway to determine if these channels can be used as drug targets to reverse declines in male urogenital function. Furthermore, developing safe and efficacious TRP channel modulators is warranted for male urogenital disorders in a clinical setting.

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Impact of a folic acid-enriched diet on urinary tract function in mice treated with testosterone and estradiol

Cited by 16 publications

References 37 publications

In Uteroand Lactational TCDD Exposure Increases Susceptibility to Lower Urinary Tract Dysfunction in Adulthood

In Uteroand Lactational TCDD Exposure Increases Susceptibility to Lower Urinary Tract Dysfunction in Adulthood

A folic acid‐enriched diet attenuates prostate involution in response to androgen deprivation

Potential therapeutic value of transient receptor potential channels in male urogenital system

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