Absence of Cyclic Adenosine 3′:5′ Monophosphate Responsive Element Modulator Expression at the Spermatocyte Arrest Stage

Abstract

Objective: To test the hypotheses that variations in the expression of adenosine 3′:5′ monophosphate (cAMP) responsive element modulator are found in human seminiferous epithelium in men with impaired testicular function and subsequent infertility and that variations in apoptosis frequency are associated with differential cAMP responsive element modulator expression in male infertility states. Design: Standard immunohistochemical staining using a rabbit polyclonal antibody against the τ isoform of the cAMP responsive element modulator protein was performed on 5-μM sections of Bouin’s fixed, paraffin-embedded testicular tissue obtained from azoospermic or severely oligozoospermic men for routine clinical purposes. Histologic diagnosis was confirmed with computerized image analysis of Feulgen-stained sections. Setting: Tertiary male infertility referral center at a medical school. Patient(s): Forty-eight testis biopsies were performed in 38 azoospermic or severely oligozoospermic males. Intervention(s): Rabbit polyclonal cAMP responsive element modulator τ antibody was applied to the paraffin-embedded testis sections. Main Outcome Measure(s): Testis immunoreactivity to polyclonal cAMP responsive element modulator τ antibody and apoptotic indices. Result(s): Although cAMP responsive element modulator immunoreactivity was present in the round spermatid stage of meiosis in testis biopsy specimens showing normal spermatogenesis, spermatid maturation arrest, and hypospermatogenesis, there was complete absence of expression in biopsy specimens from patients with Sertoli cell only and spermatocyte maturation arrest states. In addition, significantly increased apoptotic indices were observed in the spermatocyte maturation arrest state in comparison with normal spermatogenesis and Sertoli cell only pattern. Conclusion(s): These data suggest that cAMP responsive element modulator may be important for spermatid development and a stage-specific regulator of human spermatogenesis. Absence of cAMP responsive element modulator may be a cause of testicular failure in various types of male infertility.