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Vol. 36. Issue 5.
Pages 282-288 (May 2012)
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Vol. 36. Issue 5.
Pages 282-288 (May 2012)
Original article
Increased expression of hypoxia-inducible factor-1α and connective tissue growth factor accompanied by fibrosis in the rat testis of varicocele
Expresión aumentada del factor inducible por hipoxia 1α y del factor de crecimiento del tejido conectivo acompañando a fibrosis en testículos de ratas con varicocele
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J.S. Paicka, K. Parka, S.W. Kima, J.W. Parkb, J.J. Kimc, M.S. Kimd, J.Y. Parkc,??
Corresponding author
jaeyoungpark@korea.ac.kr

Corresponding author.
a Department of Urology, Seoul National University College of Medicine, Seúl, Republic of Korea
b Department of Phamacology, Seoul National University College of Medicine, Seúl, Republic of Korea
c Department of Urology, Korea University College of Medicine, Seúl, Republic of Korea
d Department of Phamacology, Gachon Medical School, Incheon, Republic of Korea
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Table 1. Diameters of the seminiferous tubules.
Table 2. Valoración de la fibrosis testicular mediante análisis de imágenes.
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Abstract
Objective

We investigated hypoxia inducible factor-1α (HIF-1α), connective tissue growth factor (CTGF) expression and fibrosis in the testis of rats with surgically induced varicocele.

Materials and methods

A total of 47 adult male Sprague-Dawley rats were arranged in 3 groups, namely group 1 (varicocele operation 4 weeks ago, n=10; sham operation 4 weeks ago, n=5), group 2 (8 weeks, n=11; n=5), and group 3 (12 weeks, n=11; n=5). The rats in every group underwent bilateral orchiectomy 4, 8, and 12 weeks after the operations, respectively. HIF-1α and CTGF expression of both testes in group 3 were studied by real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Fibrotic change was assessed by quantitative image analysis.

Results

HIF-1α mRNA expression in testes tissues in varicocele operation and sham controls showed no significant differences in RT-PCR. However, CTGF mRNA expressions in left testes were found to be significantly different between varicocele operation and sham controls. HIF-1α staining was present in both testes of all specimens and CTGF staining was present in 10 left and 8 right testes of 11 specimens. However HIF-1α and CTGF staining were absent in control group. There were significant fibrotic changes of both testes in groups 2 and 3. There were significant differences in fibrotic change along the durations of surgical varicocele.

Conclusions

This study reveals that experimental varicocele in the rat is associated with HIF-1α and CTGF expression and it is accompanied by fibrotic change in the testis.

Keywords:
Alpha subunit
Connective tissue growth factor
Fibrosis
Hypoxia inducible factor 1
Varicocele
Resumen
Objetivo

Investigamos la expresión del factor inducible por hipoxia 1α (HIF-1α) del factor de crecimiento del tejido conectivo (CTGF) y la fibrosis en los testículos de ratas con varicoceles inducidos quirúrgicamente.

Material y métodos

Se distribuyó un total de 47 ratas Sprague-Dawley adultas en tres grupos: el grupo 1 (4 semanas postcirugía de varicocele, n=10; 4 semanas postcirugía simu-lada, n=5), el grupo 2 (8 semanas, n=11; n=5) y el grupo 3 (12 semanas, n=11; n=5). Todas las ratas de sendos grupos fueron sometidas a una orquiectomía bilateral a las 4, 8 y 12 semanas de la operación respectivamente. Se estudió la expresión del HIF-1α y CTGF de ambos testículos en el grupo 3 mediante RT-PCR e inmunohistoquímica. Se midió los cambios fibróticos mediante análisis cuantitativo de imágenes.

Resultados

La expresión de HIF-1α mARN en los tejidos testiculares, tanto de la operación de varicocele como de los controles, no mostró diferencias significativas en la RT-PCR. Sin embargo, las expresiones de mARN de CTGF testicular fueron significativamente diferentes entre los de la cirugía de varicocele y los controles. Hubo tinción de HIF-1α en ambos testículos de todos los especímenes y tinción de CTGF en 10 testículos izquierdos y 8 derechos de 11 especímenes. Sin embargo, no hubo tinción de HIF-1α ni de CTGF en el grupo de control. Hubo cambios fibróticos significativos de ambos testículos en los grupos 2 y 3. Hubo diferencias significativas en el cambio fibrótico según la duración del varicocele.

Conclusiones

Este estudio revela que el varicocele experimental en la rata se asocia con expresión de HIF-1α y CTGF además de cambios fibróticos en los testículos.

Palabras clave:
Subunidad alfa
Factor de crecimiento del tejido conectivo
Fibrosis
Factor inducible por hipoxia 1
Varicocele

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