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Oral Bisphenol A (BPA) given to rats at moderate doses is associated with erectile dysfunction, cavernosal lipofibrosis and alterations of global gene transcription

International Journal of Impotence Research volume 26, pages 67–75 (2014)Cite this article

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Abstract

Bisphenol A (BPA), a suspected reproductive biohazard and endocrine disruptor, released from plastics is associated with ED in occupationally exposed workers. However, in rats, despite the induction of hypogonadism, apoptosis of the penile corporal smooth muscle (SM), fat infiltration into the cavernosal tissue and changes in global gene expression with the intraperitoneal administration of high dose BPA, ED was not observed. We investigated whether BPA administered orally rather than intraperitoneally to rats for longer periods and lower doses will lead to ED. Main outcome measures are ED, histological, and biochemical markers in rat penile tissues. In all, 2.5-month-old rats were given drinking water daily without and with BPA at 1 and 0.1 mg kg–1 per day. Two months later, erectile function was determined by cavernosometry and electrical field stimulation (EFS) and serum levels of testosterone (T), estradiol (E2) and BPA were measured. Penile tissue sections were assayed by Masson (SM/collagen), Oil Red O (fat), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) (apoptosis), immunohistochemistry for Oct4 (stem cells), and α-SM actin/calponin (SM and myofibroblasts), applying quantitative image analysis. Other markers were assayed by western blotting. DNA microarrays/microRNA (miR) assays defined transcription profiles. Orally administered BPA did not affect body weight, but (1) decreased serum T and E2; (2) reduced the EFS response and increased the drop rate; (3) increased within the corporal tissue the presence of fat, myofibroblasts and apoptosis; (4) lowered the contents of SM and stem cells, but not nerve terminals; and (5) caused alterations in the transcriptional profiles for both mRNA and miRs within the penile shaft. Long-term exposure of rats to oral BPA caused a moderate corporal veno-occlusive dysfunction (CVOD), possibly due to alterations within the corporal tissue that pose gene transcriptional changes related to inflammation, fibrosis and epithelial/mesenchymal transition (EMT).

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Acknowledgements

This work was supported by grant NIH-NIEHS R21ES019465 and partially by grant NIH-NIEHS 1U01ES020887, to NGC.

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Authors and Affiliations

  1. Division of Urology, Department of Surgery, Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute, Torrance, CA, USA

    I Kovanecz, R Gelfand, M Masouminia, S Gharib, D Segura, D Vernet, J Rajfer & N F Gonzalez-Cadavid

  2. Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    I Kovanecz, J Rajfer & N F Gonzalez-Cadavid

  3. Division of Endocrinology, Charles Drew University of Medicine and Science, Los Angeles, CA, USA

    R Gelfand, D Vernet & N F Gonzalez-Cadavid

  4. Department of Health Research and Policy, Stanford University, Stanford, CA, USA

    D K Li

  5. Division of Research, Kaiser Permanente, Oakland, CA, USA

    D K Li

  6. New York State Department of Health, Wadsworth Center, Albany, NY, USA

    K Kannan

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  1. I Kovanecz
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Correspondence to N F Gonzalez-Cadavid.

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Kovanecz, I., Gelfand, R., Masouminia, M. et al. Oral Bisphenol A (BPA) given to rats at moderate doses is associated with erectile dysfunction, cavernosal lipofibrosis and alterations of global gene transcription. Int J Impot Res 26, 67–75 (2014). https://doi.org/10.1038/ijir.2013.37

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