Disease relevance of PRM2

• We therefore investigated whether male infertility could be related to the amount of Prm1 and Prm2 mRNA by applying real time quantitative PCR following RNA extraction from routinely Bouin-fixed and paraffin-embedded testicular biopsies [1].
• Changes in the expression of P1 and P2 protamines have been found to be associated with infertility in man [2].
• CONCLUSION(s): Expression of the protamine-2 gene may be a useful molecular marker to predict the presence of testicular sperm in patients with nonobstructive azoospermia [3].
• We have identified several potential prostate cancer antigens with predominantly testis-specific expression in normal tissues, including MAD-CT-1 (protamine 2) and MAD-CT-2 [4].

High impact information on PRM2

• We have examined the chromatin structure of members of the beta-globin gene family, which are expressed at different times in development, and the protamine 2 gene, which is expressed in spermatids prior to the widespread displacement of histones by transition proteins [5].
• A (GA)n repeat polymorphism in the human protamine 2 (PRM 2) gene [6].
• To address this tenet, we examined the chromatin structure of the human PRM1--> PRM2--> TNP2 domain using a PCR-based assay [7].
• PRM2 is a histone-like protein essential to spermatogenesis and was previously reported to be a likely target of sexual selection in humans and chimpanzees [8].
• Translin has also been identified as a component of a gel-shift complex detected using an RNA oligonucleotide probe, derived from the 3' UTR of protamine-2 mRNA [9].

Biological context of PRM2

• The prevalence of these SNPs was similar in both infertile patients and in proven-fertile volunteers, except that the c248t alteration in the PRM2 gene induced a nonsense codon under conditions of heterozygosity in one infertile patient [10].
• The expression of the PRM1, PRM2, and TNP2 genes facilitates the compaction and condensation of the genetic material within the developing spermatid [11].
• An overall consensus sequence for the PRM (PRM1 and PRM2) is derived by allowing aromatic and aliphatic residues to be considered hydrophobic (psi): psi-X-X-X-Al-Pro-X-Pro [12].
• The promoter regions of the clustered human spermatid-specific nucleoprotein PRM1, PRM2 arid TNP2 genes were compared to define regulatory elements that may govern their expression [13].
• Furthermore, chi2 analysis revealed a significant increase in the incidence of marked DNA fragmentation in patients with diminished levels of either P1 or P2 [14].

Anatomical context of PRM2

• The cellular expression of PRM1 and PRM2 mRNAs in single testicular spermatids from 41 azoospermic patients (in whom testicular spermatozoa were subsequently recovered and submitted for TESE-ICSI) was determined by radioactive in situ hybridization [15].
• CONCLUSION(S): In the present patient the breakpoint at 16p13.3 could have disrupted or harbored the PRM1, PRM2, or TNP2 genes responsible for the replacement of the histones involved in packaging the DNA into the sperm head [16].
• However, these round spermatids did not express PRM2 [17].
• PRM1, PRM2, and TNP2 transcripts were abundant in association with round and elongating spermatids, located in the adluminal region of the seminiferous epithelium [11].
• Sequence and restriction analyses of the corresponding fragments have confirmed that transcripts of proacrosin and protamine 2 are present in the lymphocytes not only of males, but also of adult females [18].

Associations of PRM2 with chemical compounds

• Previously, we have shown that the human PRM1 --> PRM2 --> TNP2 locus exists as a single chromatin domain bounded by two male germ cell-specific MARs, i.e. Matrix Attachment Regions [19].
• Sperm chromatin decondensation following exposure to heparin sulfate was significantly increased in patients without a measurable P2 band [20].
• DESIGN: Analysis of samples with a marked reduction in the protamine P2 content using polyacrylamide gel electrophoresis and subsequent detection of protamine P2 precursors through Western blot analysis [21].
• In the case of human protamine P2, the strong retention on the IDA-Zn(II) column seems to result from the additive contribution of all the histidine residues of the molecule [22].
• Treatment with alkaline phosphatase identified those four proteins as phosphorylated protamines, and cyanogen bromide (CNBr) treatment of the dephosphorylated protamines distinguished them as variants of protamine 2 and not of protamine 1 [23].

Other interactions of PRM2

• The relationship between PRM1 and PRM2 transcript levels and the TESE-ICSI outcome was evaluated [15].
• We assume that the disturbances in the sperm chromatin condensation of our patients, and those described in the literature, are not primarily due to mutations in the genes for PRM1, PRM2 and TNP1 [24].
• A preliminary report on the implication of RT-PCR detection of DAZ, RBMY1, USP9Y and Protamine-2 mRNA in testicular biopsy samples from azoospermic men [25].
• The results show that human protamine 3 elutes first, closely followed by protamine 2 [26].
• While enterokinase revealed PCR signals solely for Prm2, no amplification signal was obtained using chymotrypsin [27].

Analytical, diagnostic and therapeutic context of PRM2

• Protamines are low molecular weight, highly basic nuclear proteins involved in the condensation of sperm chromatin. cDNA clones for human protamine 1 and 2 (PRM1 and PRM2) were used for Northern blot experiments with RNA from different human tissues [28].
• Semi-quantitative real-time RT-PCR was used to quantify P1 and P2 mRNA levels [29].
• RESULT(S): After selection of the samples with a marked reduction of the protamine P2 content and subsequent analysis by Western blot, a small proportion of putative P2 precursors was detected in most samples, whereas a significant increase was detected in two of them [21].
• Twelve patients with no measurable P2 underwent intracytoplasmic sperm injection (ICSI), with 6 patients (6/12, 50%) becoming pregnant [20].
• These results suggested that rat type-A spermatogonial cells underwent meiosis during the primary co-culture with the Sertoli cells, based on morphology, flow cytometry and PRM-2 expression, but the normality of the spermatid-like cells was not supported by microinsemination and TP1/2 expression [30].

References