821 BISPHENOL A ADMINISTERED ORALLY AT MODERATE DOSES INDUCES ERECTILE DYSFUNCTION AND CAVERNOSAL LIPO-FIBROSIS IN RATS (2013)

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research (I)1 Apr 2013821 BISPHENOL A ADMINISTERED ORALLY AT MODERATE DOSES INDUCES ERECTILE DYSFUNCTION AND CAVERNOSAL LIPO-FIBROSIS IN RATS Istvan Kovanecz, Sahir Gharib, Dolores Vernet, Denesse Segura, Maryam Masouminia, Jacob Rajfer, De-Kun Li, Kurunthachalam Kannan, and Nestor Gonzalez-Cadavid Istvan KovaneczIstvan Kovanecz Torrance, CA , Sahir GharibSahir Gharib Torrance, CA , Dolores VernetDolores Vernet Torrance, CA , Denesse SeguraDenesse Segura Torrance, CA , Maryam MasouminiaMaryam Masouminia Torrance, CA , Jacob RajferJacob Rajfer Los Angeles, CA , De-Kun LiDe-Kun Li Oakland, CA , Kurunthachalam KannanKurunthachalam Kannan Albany, NY , and Nestor Gonzalez-CadavidNestor Gonzalez-Cadavid Los Angeles, CA View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.387AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bisphenol A (BPA), a suspected reproductive biohazard/endocrine disruptor released from plastics and dental sealants, has been associated with erectile dysfunction (ED) in exposed workers. However, in male rats, daily intraperitoneal administration of BPA for 3 months induced hypogonadism, mild cavernosal lipo-fibrosis and changes in global gene expression, but not ED. We aimed to investigate in the rat model whether BPA at lower doses but given orally for longer periods would cause a more severe cavernosal tissue alteration and ED. METHODS 2.5-month old male rats (kept in BPA free housing) were given BPA at 1 and 0.1 mg/kg/day in the drinking water, or water alone (n=8/group). Erectile function was assayed at 4 months by cavernosometry and electrical field stimulation (EFS). Testosterone (T), estradiol (E2), and BPA (by HPLC-ESI-MS/MS) were measured in blood. Penile shaft tissue sections were assayed by Masson trichrome (fibrosis), Oil Red O (fat deposition), TUNEL (apoptosis), immunohistochemistry of calponin/α-SM actin (ASMA) (smooth muscle cells (SMC) and myofibroblasts), and stem cells by nuclear Oct 4, followed by quantitative image analysis. Western blots evaluated SMC by ASMA, and neural content by NF-70 and nNOS. RESULTS BPA did not affect body weights, but the 1 mg/kg/day dose induced the following statistically significant changes in comparison to untreated controls: 1) total BPA in serum was increased 10.8 fold; 2) serum T and E2 were reduced by 50% and 88%, respectively, 3) the drop rate by cavernosometry increased by 67% and the EFS response was reduced by 11%; 4) the fat deposition and apoptotic index increased by 3.8 fold and 12%, respectively; 5) the SMC/collagen ratio, and the calponin and ASMA contents, were reduced by 48%, 60%, and 39%, respectively; 6) the stem cell content was reduced by 88%; 7) the ASMA content by western blot was also reduced, but there were no significant changes in nitrergic neural markers. The 0.1 mg/kg/day dose exerted lower changes, except for the drop rate that was doubled, and the apoptotic index that was not changed. CONCLUSIONS Long-term oral exposure of rats to BPA, at doses nearly equivalent to the ones calculated for the BPA exposed workers with ED, causes a moderate corporal veno-occlusive dysfunction (CVOD), possibly due to lipofibrosis, and loss of SMC within the corporal tissue. These preliminary data suggest that BPA may have a direct effect on the corporal tissue itself but studies using lower doses and longer periods of exposure are needed to fully assess its environmental effects. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e337 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Istvan Kovanecz Torrance, CA More articles by this author Sahir Gharib Torrance, CA More articles by this author Dolores Vernet Torrance, CA More articles by this author Denesse Segura Torrance, CA More articles by this author Maryam Masouminia Torrance, CA More articles by this author Jacob Rajfer Los Angeles, CA More articles by this author De-Kun Li Oakland, CA More articles by this author Kurunthachalam Kannan Albany, NY More articles by this author Nestor Gonzalez-Cadavid Los Angeles, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...