Developmental Evaluation of Aldo-keto Reductase 1C3 Expression in the Cryptorchid Testis

Objectives To characterize aldo-keto reductase 1C3 (AKR1C3) expression in surgically-removed cryptorchid testes. Human AKR1C3 is a monomeric, cytoplasmic, multifunctional enzyme that reduces ketosteroids, ketoprostaglandins, and lipid aldehydes. AKR1C3 expression has been demonstrated in normal adult Leydig cells and peritubular fibromyocytes. No prior studies have evaluated AKR1C3 expression patterns across different age groups. Methods Surgically excised cryptorchid testes were subjected to hematoxylin-eosin evaluation to review overall testicular pathology. These samples were then evaluated for AKR1C3 distribution via immunohistochemical staining with a monospecific AKR1C3 monoclonal antibody. Single-pathologist grading of AKR1C3 expression was correlated with clinical presentations. Results A total of 16 cryptorchid testes were identified from the 2000 to present. Median age at the time of surgery was 9 years (range, 1-17). The testes were excised due to atrophy, poor tissue consistency, and short spermatic cord length. AKR1C3 expression was identified at all ages in fibromyocytes surrounding the testicular tubules. Leydig cell expression was absent at Tanner stages 1 and 2, while strong expression was found at Tanner stage 3 and beyond. No AKR1C3 expression was seen in germ cells at any stage. AKR1C3 expression was identified in 18%-26% of Sertoli cells in patients at Tanner stages 2 and beyond. Conclusions AKR1C3 expression occurs in a Tanner stage dependent-fashion. Pre- and peri-pubertal changes appear to promote expression of the enzyme in Leydig cells. In contrast to the normal adult testis, the pediatric cryptorchid testis reveals AKR1C3 expression in Sertoli cells. Additional studies are warranted to determine the involvement of AKR1C3 in testicular descent and development.