Round spermatids show normal testis-specific H1t but reduced cAMP-responsive element modulator and transition protein 1 expression in men with round-spermatid maturation arrest

During spermiogenesis, histones are replaced by transition proteins, which in turn are replaced by protamines. The TNP1 gene-encoding TP1 (transition protein 1) protein contains a cAMP-responsive element (CRE) that serves as binding site for the CRE modulator (CREM). To gain further insight into the complex regulation of nucleoprotein exchanges in haploid spermatids and it s potential role for spermatogenic impairment. we studied the gene expressi on of testis-specific histone Hit, CREM, and TNP1 in testicular biopsies fr om men with normal spermatogenesis (n = 20) and with round spermatid matura tion arrest (n = 16). During normal spermatogenesis, Hit messenger RNA (mRN A) was present in 86.2% +/- 8.7% of pachytene spermatocytes (stages III-V), whereas Hit protein was synthesized in 83.5% +/- 13.0% of pachytene sperma tocytes (stages III-V) and persisted in 95.2% +/- 3.1% of spermatids (steps 1-5). CREM mRNA was detectable in 74.2% +/- 9.4% of pachytene spermatocyte s (stages IV-V) and in 78.7% +/- 10.0% of spermatids (steps 1-3). CREM prot ein was synthesized in 81.2% +/- 14.2% of spermatids (steps 1-3). TNP1 mRNA was present in 80.0% +/- 13.5% of spermatids (steps 2-4), whereas TP1 prot ein was synthesized in 89.7% +/- 5.3% of spermatids (steps 3-4). In men wit h round spermatid maturation arrest, spermatids only develop to step 3 of d ifferentiation. These spermatids were devoid of both CREM and TP1 but did c ontain Hit. These results indicate that TPI is likely to be an important pa rameter in the histone-to-protamine exchange and in the initiation of sperm atid elongation. CREM is involved in the regulation of TNP1 gene expression and consequently plays a vital role in the correct differentiation step fr om round spermatids to mature spermatozoa.