Seyedmehdi Nourashrafeddin
University of Pittsburgh School of Medicine, USA
Title: Stage-specific expression of CYP26B1 in the adult testis is responsible for pulsatile retinoic acid signaling in spermatogenesis
Biography
Biography: Seyedmehdi Nourashrafeddin
Abstract
Background: The major physiologically active form of vitamin A, Retinoic acid (RA), plays important roles in germ cell development in both male and female. Studies of mice deficient in the RA degradation enzyme, CYP26B1, indicated that RA is responsible for meiotic initiation; however, the mechanisms underlying the pulsatile RA signaling in spermatogenesis has not been understood yet. We studied the localization and expression analysis of CYP26B1 during development of rhesus monkey testis in order to better understanding of the mechanisms of RA signaling in spermatogenesis process.
Methods: Quantitative real-time PCR (qPCR) and immunohistochemistry was performed to determine the profile expression of CYP26B1 at both mRNA and protein levels in the juvenile and adult rhesus monkey.
Results: The expression of CYP26B1 mRNA was down-regulated during the development of monkey testis. As described previously, the CYP26B1 protein was detected in the cytoplasm of undifferentiated spermatogonia in the developing testis. A rather heterogeneous pattern of the CYP26B1 protein expression was observed along the different stages of seminiferous epithelium, indicating the expression of the protein is stage specific. In adult testes, the highest level of CYP26B1 protein was found in in differentiating germ cells within seminiferous epithelial stages X-XII. The peak of CYP26B1 protein expression was coincided with the onset of meiosis and observed in preleptotene and early leptotene spermatocytes. Whereas, lowest level of CYP26B1 expression was observed in stages VI-IX of the seminiferous epithelium, where undifferentiated Type A spermatogonia divide and differentiate to Type B spermatogonia, meiosis initiates and spermiogenesis occurs.
Conclusion: Down-regulation of CYP26B1 mRNA during the development of monkey testis is consistent with initiation of meiosis in the adult testis. However, the stage-specific expression of RA degradation enzyme CYP26B1 in the seminiferous tubules of adult testis led us to suggest that it might be responsible for pulsatile RA signaling in spermatogenesis. These findings presumably support that the elevated amount of RA in the undifferentiated Type A spermatogonia during stages VI-IX of the seminiferous epithelium of the adult testis is responsible for differentiation of spermatogonia and meiosis entry.