Alterations of gene profiles in Leydig-cell-regenerating adult rat testis after ethane dimethane sulfonate-treatment

• Published in: Asian journal of andrology Vol. 17; no. 2; pp. 253 - 260
• Main Authors: Zhang, Yu-Fei, Yuan, Kai-Ming, Liang, Yong, Chu, Yan-Hui, Lian, Qing-Quan, Ge, Yu-Fei, Zhen, Wei, Sottas, Chantal M, Su, Zhi-Jian, Ge, Ren-Shan
• Format: Journal Article
• Language: English
• Published: China Medknow Publications and Media Pvt. Ltd 01-03-2015; Medknow Publications & Media Pvt. Ltd; Medknow Publications & Media Pvt Ltd; Wolters Kluwer Medknow Publications
• Subjects: Animals; Antispermatogenic Agents - pharmacology; Aryl Hydrocarbon Hydroxylases - genetics; Aryl Hydrocarbon Hydroxylases - metabolism; Cytochrome P450 Family 2; Endoplasmic reticulum; Enzymes; ethane dimethane sulfonate; gene profiling; Leydig cell; steroidogenesis; Gene expression; Gene Expression Profiling; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Genetic aspects; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; Leydig Cells - cytology; Leydig Cells - drug effects; Leydig Cells - metabolism; Male; Mesylates - pharmacology; Microarray Analysis; Models, Animal; Original; Physiological aspects; Proteins; Rats; Rats, Sprague-Dawley; Regeneration - drug effects; Regeneration - physiology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Stem cells; Steroid Hydroxylases - genetics; Steroid Hydroxylases - metabolism; Testis; Testis - cytology; Testis - drug effects; Testis - metabolism; Testosterone; Testosterone - genetics; Testosterone - metabolism; United States; China
• ISSN: 1008-682X; 1745-7262
• DOI: 10.4103/1008-682X.136447

Only occupying about 1%-5% of total testicular cells, the adult Leydig cell (ALC) is a unique endocrine cell that produces androgens. Rat Leydig cells regenerate after these cells in the testis are eliminated with ethane dimethane sulfonate (EDS). In this study, we have characterized Leydig cell regeneration and messenger ribonucleic acids (mRNA) profiles of EDS treated rat testes. Serum testosterone, testicular gene profiling and some steroidogenesis-related proteins were analyzed at 7, 21, 35 and 90 days after EDS treatment. Testicular testosterone levels declined to undetectable levels until 7 days after treatment and then started to recover. Seven days after treatment, 81 mRNAs were down-regulated greater than or equal to two-fold, with 48 becoming undetectable. These genes increased their expression 21 days and completely returned to normal levels 90 days after treatment. The undetectable genes include steroidogenic pathway proteins: steroidogenic acute regulatory protein, Scarb1, Cyp11a1, Cyp17a1, Hsd3b1, Cyp1b1 and Cyp2a1. Seven days after treatment, there were 89 mRNAs up-regulated two-fold or more including Pkib. These up-regulated mRNAs returned to normal 90 days after treatment. Cyp2a1 did not start to recover until 35 days after treatment, indicating that this gene is only expressed in ALCs not in the precursor cells. Quantitative polymerase chain reaction, western blotting and semi-quantitative immunohistochemical staining using tissue array confirmed the changes of several randomly picked genes and their proteins.