A Mouse Strain Less Responsive to Dioxin-Induced Prostaglandin E2 Synthesis Is Resistant to the Onset of Neonatal Hydronephrosis

Aida-Yasuoka, Keiko; Yoshioka, Wataru; Kawaguchi, Tatsuya; Ohsako, Seiichiroh; Tohyama, Chiharu

doi:10.1093/toxsci/kfu142

Cited by 8 publications

(7 citation statements)

References 57 publications

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“…We showed that IUL TCDD exposure, followed by adult T þ E 2 treatment, increased kidney wet weight and incidence of frank hydronephrosis. It should be noted that others have demonstrated IUL TCDD exposure induces upper urinary tract dysfunction including fetal hydronephrosis (Aida-Yasuoka et al, 2014;Moore et al, 1973). We did not observe frank hydronephrosis in mice exposed to TCDD without adult exogenous hormone exposure.…”

Section: Discussioncontrasting

confidence: 51%

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: Discussioncontrasting

confidence: 51%

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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“…The role of AQP2 in the onset of hydronephrosis is not clear because there are some inconsistent observations on the abundance of AQP2 and its localization in the different experiments, such as pharmacological inhibition of V2R (5), nonsense mutation of V2R (58), and our present ( Fig. 4) and previous studies (2,35,55). Studies on short-term regulation and long-term adaptation of apical-trafficking, endocytosis, and expression of AQP2 may elucidate the underlying mechanism.…”

Section: F757mentioning

confidence: 51%

“…4, C and F) (2), resulting in a decrease in water permeability at the collecting duct (17,34) to produce dilute urine (Fig. 4A) (2). Hydronephrosis accompanied with polyuria and low urine osmolality has been reported in another mouse model of a disrupted renal AVP system (58), in which renal V2 vasopressin receptor (V2R) is genetically ablated by a nonsense mutation.…”

Section: F757mentioning

confidence: 95%

Polyuria-associated hydronephrosis induced by xenobiotic chemical exposure in mice

Yoshioka

Kawaguchi

Nishimura

et al. 2016

American Journal of Physiology-Renal Physiology

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Hydronephrosis is a commonly found disease state characterized by the dilation of renal calices and pelvis, resulting in the loss of kidney function in the severest cases. A generally accepted etiology of hydronephrosis involves the obstruction of urine flow along the urinary tract. In the recent years, we have developed a mouse model of hydronephrosis induced by lactational exposure to dioxin and demonstrated a lack of anatomical obstruction in this model. We also showed that prostaglandin E synthesis system plays a critical role in the onset of hydronephrosis. In the present study, we found that neonatal hydronephrosis was not likely to be associated with functional obstruction (impaired peristalsis) but was found to be associated with polyuria and low urine osmolality with the downregulation of proteins involved in the urine concentrating process. The administration of an antidiuretic hormone analog to the dioxin-exposed pups not only suppressed the increased urine output but also decreased the incidence and severity of hydronephrosis. In contrast to the case in pups, administration of dioxin to adult mice failed to induce polyuria and upregulation of prostaglandin E synthesis system, and the adult mice were resistant to develop hydronephrosis. These findings suggest the possibility that polyuria could induce hydronephrosis in the absence of anatomical or functional obstruction of the ureter. It is concluded that the present animal model provides a unique example of polyuria-associated type of hydronephrosis, suggesting a need to redefine this disease state.

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“…Signaling downstream of PGE 2 leading to TiNH remains to be elucidated. A plausible mechanism is that increased PGE 2 in the renal tubules interferes with the water reabsorption system [59,60,61], resulting in a decrease in water permeability [60,61] to produce diluted urine [46,62]; consequently, the increased urine volume [46] overwhelms the ureter propelling capacity and causes backpressure in the kidney pelvicalyceal space.…”

Section: Hydronephrosismentioning

confidence: 99%

“…Little is known about additional factors determining sensitivity to TCDD toxicity. C57BL/6J and BALB/cA mice exhibit a substantial difference in the sensitivity to TiNH, although both strains possess AhRs with high affinity to TCDD [62]. This difference is attributed to the lower responsiveness of mPGES-1 expression to TCDD exposure in the kidney of BALB/cA pups.…”

Section: Hydronephrosismentioning

confidence: 99%

Mechanisms of Developmental Toxicity of Dioxins and Related Compounds

Yoshioka

Tohyama

2019

IJMS

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Dioxins and related compounds induce morphological abnormalities in developing animals in an aryl hydrocarbon receptor (AhR)-dependent manner. Here we review the studies in which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is used as a prototypical compound to elucidate the pathogenesis of morphological abnormalities. TCDD-induced cleft palate in fetal mice involves a delay in palatogenesis and dissociation of fused palate shelves. TCDD-induced hydronephrosis, once considered to be caused by the anatomical obstruction of the ureter, is now separated into TCDD-induced obstructive and non-obstructive hydronephrosis, which develops during fetal and neonatal periods, respectively. In the latter, a prostaglandin E2 synthesis pathway and urine concentration system are involved. TCDD-induced abnormal development of prostate involves agenesis of the ventral lobe. A suggested mechanism is that AhR activation in the urogenital sinus mesenchyme by TCDD modulates the wingless-type MMTV integration site family (WNT)/β-catenin signaling cascade to interfere with budding from urogenital sinus epithelium. TCDD exposure to zebrafish embryos induces loss of epicardium progenitor cells and heart malformation. AHR2-dependent downregulation of Sox9b expression in cardiomyocytes is a suggested underlying mechanism. TCDD-induced craniofacial malformation in zebrafish is considered to result from the AHR2-dependent reduction in SRY-box 9b (SOX9b), probably partly via the noncoding RNA slincR, resulting in the underdevelopment of chondrocytes and cartilage.

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A Mouse Strain Less Responsive to Dioxin-Induced Prostaglandin E2 Synthesis Is Resistant to the Onset of Neonatal Hydronephrosis

Cited by 8 publications

References 57 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

Polyuria-associated hydronephrosis induced by xenobiotic chemical exposure in mice

Mechanisms of Developmental Toxicity of Dioxins and Related Compounds

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