Interactive Effects of Perinatal BPA or DES and Adult Testosterone and Estradiol Exposure on Adult Urethral Obstruction and Bladder, Kidney, and Prostate Pathology in Male Mice

Abstract

Obstructive voiding disorder (OVD) occurs during aging in men and is often, but not always, associated with increased prostate size, due to benign prostatic hyperplasia (BPH), prostatitis, or prostate cancer. Estrogens are known to impact the development of both OVD and prostate diseases, either during early urogenital tract development in fetal–neonatal life or later in adulthood. To examine the potential interaction between developmental and adult estrogen exposure on the adult urogenital tract, male CD-1 mice were perinatally exposed to bisphenol A (BPA), diethylstilbestrol (DES) as a positive control, or vehicle negative control, and in adulthood were treated for 4 months with Silastic capsules containing testosterone and estradiol (T+E2) or empty capsules. Animals exposed to BPA or DES during perinatal development were more likely than negative controls to have urine flow/kidney problems and enlarged bladders, as well as enlarged prostates. OVD in adult T+E2-treated perinatal BPA and DES animals was associated with dorsal prostate hyperplasia and prostatitis. The results demonstrate a relationship between elevated exogenous estrogen levels during urogenital system development and elevated estradiol in adulthood and OVD in male mice. These findings support the two-hit hypothesis for the development of OVD and prostate diseases.

In utero and lactational PCB exposure drives anatomic changes in the juvenile mouse bladder

“…The ability of environmental chemicals, especially during development, to impact urinary function throughout life is an area of increasing interest ( Ricke et al, 2016 , Taylor et al, 2020 , Turco et al, 2020 ). Others have found links between 2,3,7,8-tetrachlorodibenzodioxin (dioxin or TCDD) and impaired lower urinary tract function ( Ricke et al, 2016 , Turco et al, 2020 ).…”

Polychlorinated Biphenyls (PCBs): Risk Factors for Autism Spectrum Disorder?

“…The hypothesis that environmental factors contribute to the high rate of bladder dysfunction in ASD is strengthened by evidence that various environmental chemicals have been shown to alter urinary function in preclinical models [236][237][238]. For example, the estrogenic chemical bisphenol A has been linked to abnormal lower urinary tract function [236,239]. Several PCBs have been identified to have estrogenic activity [96], but whether they alter urinary function is unknown.…”

The Relationship between Typical Environmental Endocrine Disruptors and Kidney Disease

“…Animal studies : Histopathological evaluation of rats exposed to BPA for 30 days showed infiltrative and dilatative changes in renal tissues, leading to renal failure [ 133 , 134 , 135 ]. Significant increases in sodium, potassium and calcium concentrations were observed in response to BPA, indicating that BPA disrupts electrolyte balance, leading to renal dysfunction [ 136 , 137 ]. Fetal glomerular abnormalities and decreased glomerular formation were observed after being exposed to BPA during pregnancy [ 138 ].…”