Retinoic acid signaling biomarkers after treatment with retinoic acid and retinoic acid receptor alpha antagonist (Ro 41-5253) in canine testis: An in vitro organ culture study

作者：Kasimanickam Vanmathy R; Kasimanickam Ramanathan K^*

来源：Theriogenology, 2013, 79(1): 10-16.

DOI：10.1016/j.theriogenology.2012.09.001

• Dog testis
• ALDH1
• CYP26b1
• CRABII
• STRA8

Retinoic acid (RA) is an essential component for development and maintenance of the male genital tract and for spermatogenesis. Aldehyde dehydrogenase (ALDH)1, cytochrome P450 (CYP)26b1, RA receptor (RAR)alpha, cellular RA-binding protein (CRAB)II, and stimulated by RA gene (STRA)8 are involved in synthesis, metabolism signaling pathways, and as downstream effectors of RA. The objective was to elucidate the effects of exogenous RA and a RAR alpha antagonist on gene expression of ALDH1, CYP26b1, RAR alpha, cellular RA-binding protein II, and STRA8 in an in vitro organ culture model of canine testis. Testicular tissues from medium-sized mixed breed dogs (N = 5; age 8 +/- 0.17 mo) were subjected to exogenous all trans-RA (final concentrations of 1, 2, and 10 mu M, and DMSO as control) for 24 h. Similarly, testicular tissues were treated with Ro 41-5253 (RAR alpha antagonist), at 1, 10, and 50 mu M final concentrations (DMSO as control) for 24 h. Exogenous RA or the RAR alpha antagonist decreased (P < 0.05) mRNA abundance of ALDH1 in a dose-dependent manner compared with control. The CRABII mRNA abundance was greater after RA treatment compared with control (P < 0.01). but only 50 mu M Ro 41-5253 effectively decreased CRABII mRNA abundance compared with control (P < 0.01). Although RA did not affect RAR alpha mRNA abundance, the RAR alpha antagonist treatment lowered RAR alpha mRNA abundance compared with control (P < 0.05). Abundance of CYP26bl and STRA8 mRNA were greater (P < 0.05) after RA treatment, but lower (P < 0.05) after RAR alpha antagonist treatment compared with control. In conclusion, exogenous RA decreased mRNA abundance of ALDH1 and increased mRNA abundance of RA signaling molecules and its downstream effectors (CYP26b1, CRABII, and STRA8), whereas treatment with a RAR alpha antagonist effectively decreased RAR alpha and RA metabolism molecules and its downstream effectors in canine testis. Perhaps pharmacological intervention via the RA pathway would enable canine male contraception or treatment of testicular pathology. Published by Elsevier Inc.

• 出版日期2013-1-1