Different CREM-isoform gene expression between equine and human normal and impaired spermatogenesis.
Abstract: Histone-to-protamine exchange causes chromatin condensation ceasing gene expression in elongating spermatids. Gene expression of protamines is regulated by the transcription factor cAMP-responsive element modulator (CREM). Altered CREM expression results in male infertility, as shown by CREM-knock-out mice being sterile due to round spermatid maturation arrest and patients exhibiting round spermatid maturation arrest revealing a lack or substantial reduction of both CREM-mRNA and CREM-protein. Similar defects in histone-to-protamine exchange have been suggested in infertile stallions exhibiting enlarged sperm heads. The CREM-gene consists of 14 exons. Alternative exon splicing results in the production of both activator and repressor proteins. To further clarify the role of different CREM-isoforms for male infertility, the expression pattern of various CREM-isoforms during equine and human normal and impaired spermatogenesis was investigated by RT-PCR. Stallions with normal spermatogenesis expressed six activators and three repressors. In men three activators and seven different repressors were detected. In one stallion and patients with impaired spermatogenesis, only repressors were found. It is concluded that (i). stallion and man reveal a different CREM expression pattern, (ii). the expression of CREM activators is a prerequisite for normal spermatogenesis, and (iii). the lack of CREM activator expression results in male infertility.
Publication Date: 2003-09-27 PubMed ID: 14511788DOI: 10.1016/s0093-691x(03)00142-0Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study investigates the role of different forms of the cAMP-responsive element modulator (CREM) in normal and impaired sperm production in horses and humans. The research shows that a specific pattern of CREM expression is required for normal sperm production, and the lack of this expression results in infertility.
Understanding the cAMP-responsive element modulator (CREM)
- The study revolves around the transcription factor cAMP-responsive element modulator (CREM), which plays a pivotal role in the gene expression of protamines, proteins that are crucial in the process of spermatogenesis.
- CREM gene consists of 14 exons and through the process of alternative exon splicing, both activator and repressor proteins are produced.
- Any alterations in the expression of CREM can lead to male infertility. This was demonstrated through experiments where mice lacking CREM were shown to be sterile because their immature sperm cells could not mature further. Similar observations were made in patients who had a significant reduction or complete lack of both CREM-mRNA and CREM-protein.
Investigating CREM-isoform gene expression
- The research used reverse transcription polymerase chain reaction (RT-PCR) to study the gene expression patterns of different CREM-isoforms in horses and humans, both in instances of normal and impaired sperm production.
- It was found that stallions (male horses) with normal sperm production expressed six activator CREM-isoforms and three repressor CREM-isoforms.
- In normal human males, three activator and seven different repressor CREM-isoforms were observed.
CREM expression pattern and infertility
- In instances of impaired sperm production (one stallion and human patients), only repressor CREM-isoforms were identified.
- The researchers concluded that there is a distinct variability in the CREM expression pattern in stallions and human males.
- The study emphasizes that the expression of CREM activators is essential for normal sperm production.
- The absence of CREM activator expression consequently leads to male infertility.
Cite This Article
APA
Blöcher S, Behr R, Weinbauer GF, Bergmann M, Steger K.
(2003).
Different CREM-isoform gene expression between equine and human normal and impaired spermatogenesis.
Theriogenology, 60(7), 1357-1369.
https://doi.org/10.1016/s0093-691x(03)00142-0 Publication
Researcher Affiliations
- Institute of Veterinary Anatomy, Histology and Embryology, University of Giessen, Frankfurter Strasse 98, Giessen 35392, Germany.
MeSH Terms
- Alternative Splicing
- Animals
- Biopsy
- Cyclic AMP Response Element Modulator
- DNA-Binding Proteins / genetics
- Exons
- Gene Expression
- Gene Expression Regulation / genetics
- Horse Diseases / genetics
- Horses
- Humans
- Infertility, Male / genetics
- Infertility, Male / veterinary
- Male
- RNA, Messenger / analysis
- Repressor Proteins
- Reverse Transcriptase Polymerase Chain Reaction
- Species Specificity
- Spermatids / physiology
- Spermatogenesis / genetics
- Testis / pathology
Citations
This article has been cited 3 times.- Tanaka H, Hirose M, Tokuhiro K, Tainaka H, Miyagawa Y, Tsujimura A, Okuyama A, Nishimune Y. Molecular biological features of male germ cell differentiation.. Reprod Med Biol 2007 Mar;6(1):1-9.
- Sadamoto H, Kitahashi T, Fujito Y, Ito E. Learning-Dependent Gene Expression of CREB1 Isoforms in the Molluscan Brain.. Front Behav Neurosci 2010;4:25.
- Lardenois A, Chalmel F, Demougin P, Kotaja N, Sassone-Corsi P, Primig M. Fhl5/Act, a CREM-binding transcriptional activator required for normal sperm maturation and morphology, is not essential for testicular gene expression.. Reprod Biol Endocrinol 2009 Nov 24;7:133.
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