Testicular Testosterone and Estradiol Concentrations and Aromatase Expression in Men with Nonobstructive Azoospermia

• Published in: The journal of clinical endocrinology and metabolism 2021-04, Vol.106 (4), p.e1803-e1815
• Main Authors: Shiraishi, Koji, Oka, Shintaro, Matsuyama, Hideyasu
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Anastrozole; Aromatase; Cells; Estradiol; Immunohistochemistry; Leydig cells; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Phenols; Polymerase chain reaction; Reverse transcription; Sperm; Spermatogenesis; Testes; Testosterone
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgaa860

Abstract Context Spermatogenesis is strictly regulated by the intratesticular hormonal milieu, in which testosterone (T) and estradiol (E2) play pivotal roles. However, the optimal expression of aromatase and intratesticular T (ITT) and E2 (ITE2) levels are unknown. Objective To investigate ITT/ITE2 and aromatase expression in men with nonobstructive azoospermia (NOA) and to elucidate the roles of aromatase in spermatogenesis, as determined based on sperm retrieval by microdissection testicular sperm extraction (micro-TESE). Design and Setting A retrospective study at a reproductive center using serum, testicular specimens, and intratesticular fluid. Patients Seventy-six men with NOA, including 4 men who received 3 months of anastrozole administration prior to micro-TESE, and 18 men with obstructive azoospermia. Interventions Testicular aromatase expression was evaluated using immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (RT-PCR). Intratesticular T and ITE2 levels were determined using liquid chromatography-tandem mass spectrometry. Results Aromatase was mainly located in Leydig cells, and the levels of its transcript and protein expression levels were increased in men with NOA. No correlation was observed between serum T/E2 and ITT/ITE2 levels, whereas significant associations were observed between decreased ITT and increased ITE2, aromatase expression, and sperm retrieval. Treatment with anastrozole increased the ITT/ITE2 ratio and decreased aromatase expression. Conclusions A close association between the expression of aromatase in Leydig cells and ITT/ITE2 was shown. Leydig cell aromatase is a factor that is independently correlated with spermatogenesis, and aromatase inhibitors may open a therapeutic window by increasing ITT/ITE2 in selected patients.