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Valproic acid induces histologic changes and decreases androgen receptor levels of testis and epididymis in rats

BACKGROUND: Valproic acid (VPA), an anti-epileptic drug, can cause male subfertility. However, the degree to which testicular and epididymal histopathologies and androgen receptor (AR) expression are changed under VPA treatment has never been reported. OBJECTIVE: To investigate the histopathological...

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Autores principales: Iamsaard, Sitthichai, Sukhorum, Wannisa, Arun, Supatcharee, Phunchago, Nichapa, Uabundit, Nongnuch, Boonruangsri, Porntip, Namking, Malivalaya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Research and Clinical Center for Infertility 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555039/
https://www.ncbi.nlm.nih.gov/pubmed/28835938
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author Iamsaard, Sitthichai
Sukhorum, Wannisa
Arun, Supatcharee
Phunchago, Nichapa
Uabundit, Nongnuch
Boonruangsri, Porntip
Namking, Malivalaya
author_facet Iamsaard, Sitthichai
Sukhorum, Wannisa
Arun, Supatcharee
Phunchago, Nichapa
Uabundit, Nongnuch
Boonruangsri, Porntip
Namking, Malivalaya
author_sort Iamsaard, Sitthichai
collection PubMed
description BACKGROUND: Valproic acid (VPA), an anti-epileptic drug, can cause male subfertility. However, the degree to which testicular and epididymal histopathologies and androgen receptor (AR) expression are changed under VPA treatment has never been reported. OBJECTIVE: To investigate the histopathological changes and AR protein levels of testis and epididymis in VPA-treated rats for every single day. MATERIALS AND METHODS: Sixty-four adult male Wistar rats were divided into control and VPA-treated groups (n=8/ each). Treated rats were injected with 500 mg/ kgBW, intraperitoneally, VPA for 10 consecutive days. At the end of every experimental day, all reproductive parameters including histology by hematoxylin and eosin staining and protein expression of AR by Immuno-Western blot in testis and epididymis were examined. RESULTS: VPA-treated rats showed dramatically changes in testicular and epididymal histopathologies compared to control group. The multinucleated giant cells and sloughing of germ cells were observed on day 6. The germ cell disintegration and increased intercellular spaces of seminiferous tubular epithelium appeared in days 7-10 of VPA treatment. Additionally, extensive multinucleated giant cells and complete exfoliation were clearly found from days 8-10. Such exfoliated germ cells were clearly seen in its epididymal lumen at day 10. The increasing rate of sperm concentration was approximately 32.31% of that in control group at day 10 (p=0.03). Moreover, the protein expressions of testicular and epididymal AR (% intensity/ 80 µg protein lysate) was decreased in VPA-treated rats compared with control. CONCLUSION: VPA treatment induces histologic changes of germ cell epithelium in seminiferous tubules and decreases the expression of testicular and epididymal androgen receptors.
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spelling pubmed-55550392017-08-23 Valproic acid induces histologic changes and decreases androgen receptor levels of testis and epididymis in rats Iamsaard, Sitthichai Sukhorum, Wannisa Arun, Supatcharee Phunchago, Nichapa Uabundit, Nongnuch Boonruangsri, Porntip Namking, Malivalaya Int J Reprod Biomed Original Article BACKGROUND: Valproic acid (VPA), an anti-epileptic drug, can cause male subfertility. However, the degree to which testicular and epididymal histopathologies and androgen receptor (AR) expression are changed under VPA treatment has never been reported. OBJECTIVE: To investigate the histopathological changes and AR protein levels of testis and epididymis in VPA-treated rats for every single day. MATERIALS AND METHODS: Sixty-four adult male Wistar rats were divided into control and VPA-treated groups (n=8/ each). Treated rats were injected with 500 mg/ kgBW, intraperitoneally, VPA for 10 consecutive days. At the end of every experimental day, all reproductive parameters including histology by hematoxylin and eosin staining and protein expression of AR by Immuno-Western blot in testis and epididymis were examined. RESULTS: VPA-treated rats showed dramatically changes in testicular and epididymal histopathologies compared to control group. The multinucleated giant cells and sloughing of germ cells were observed on day 6. The germ cell disintegration and increased intercellular spaces of seminiferous tubular epithelium appeared in days 7-10 of VPA treatment. Additionally, extensive multinucleated giant cells and complete exfoliation were clearly found from days 8-10. Such exfoliated germ cells were clearly seen in its epididymal lumen at day 10. The increasing rate of sperm concentration was approximately 32.31% of that in control group at day 10 (p=0.03). Moreover, the protein expressions of testicular and epididymal AR (% intensity/ 80 µg protein lysate) was decreased in VPA-treated rats compared with control. CONCLUSION: VPA treatment induces histologic changes of germ cell epithelium in seminiferous tubules and decreases the expression of testicular and epididymal androgen receptors. Research and Clinical Center for Infertility 2017-04-10 /pmc/articles/PMC5555039/ /pubmed/28835938 Text en https://creativecommons.org/licenses/by/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Iamsaard, Sitthichai
Sukhorum, Wannisa
Arun, Supatcharee
Phunchago, Nichapa
Uabundit, Nongnuch
Boonruangsri, Porntip
Namking, Malivalaya
Valproic acid induces histologic changes and decreases androgen receptor levels of testis and epididymis in rats
title Valproic acid induces histologic changes and decreases androgen receptor levels of testis and epididymis in rats
title_full Valproic acid induces histologic changes and decreases androgen receptor levels of testis and epididymis in rats
title_fullStr Valproic acid induces histologic changes and decreases androgen receptor levels of testis and epididymis in rats
title_full_unstemmed Valproic acid induces histologic changes and decreases androgen receptor levels of testis and epididymis in rats
title_short Valproic acid induces histologic changes and decreases androgen receptor levels of testis and epididymis in rats
title_sort valproic acid induces histologic changes and decreases androgen receptor levels of testis and epididymis in rats
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555039/
https://www.ncbi.nlm.nih.gov/pubmed/28835938
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