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The human testis as a model of retinoic acid formation (1064.10)
Author(s) -
Arnold Samuel,
Kent Travis,
Schlatt Stefan,
Prasad Bhagwat Prasad,
Haenisch Michael,
Muller Chip,
Hogarth Cathryn,
Griswold Michael,
Paik Jisun,
Walsh Thomas,
Amory John,
Isoherranen Nina
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1064.10
Subject(s) - retinoic acid , sertoli cell , enzyme , spermatogenesis , limiting , seminiferous tubule , male fertility , andrology , chemistry , retinoid , biology , medicine , endocrinology , biochemistry , microbiology and biotechnology , gene , fertility , population , mechanical engineering , environmental health , engineering
Retinoic acid (RA), the active form of vitamin A (retinol), is indispensable for maintaining many essential biological processes. RA formation depends on a complex network of enzymes. The rate limiting step is irreversible formation of RA by aldehyde dehydrogenase1A (ALDH1A1‐1A3). However, the specific roles, tissue expression, and localization of these enzymes are not well understood. While RA is necessary for spermatogenesis in animal models, the source of intratesticular RA is unknown. Sertoli cell specific ALDH1A knockouts have demonstrated intratesticular RA formation is required for male fertility. Due to the requirement for intratesticular RA formation and presence of mRNA for all three ALDH1A enzymes in the human testis, the human testis was chosen as a model of the biochemistry of RA formation. In order to model RA formation, a novel LC‐MS/MS based peptide quantification method was developed to quantify ALDH1A in a cohort of 18 men. Each ALDH1A concentration was used to predict the velocity of RA formation in each donor. The accuracy of our predictions was confirmed by measuring intrinsic RA formation and RA concentrations in the same samples. Additionally, weidentified a distinct localization pattern for ALDH1A enzymes in the human testis using immunohistochemistry. In conclusion, these novel techniques were successfully used to model RA formation in human testicular tissue. In the future, RA formation in other tissues can be investigated using the assays developed. Grant Funding Source : Supported by NIH/NICHD grant U54 HD042454 and TL1TR000422