rNA in sPerm
It is well documented that spermatozoa contain a complex yet specific population of RNAs that encapsulates the gene expression of spermatogenesis. Any testicular perturbation that alters the production of spermatozoa and consequently reduces fertility should modify the spermatozoal RNA fingerprint from that of the normal. In fact, disparity in spermatozoal RNA fingerprints between fertile and infertile men ought to identify specific genetic pathways necessary for the production of fertile spermatozoa. To continue this line of investigation, studies are currently underway to compare the genetic profiles of spermatozoa obtained from normal fertile men and teratozoospermic patients.
To challenge the hypothesis that paternal RNAs are necessary for successful reproduction, a suite of spermatozoal transcripts implicated in the processes of fertilization and early embryonic development was identified. When both oocytes and early zygotes were interrogated for the presence of these transcripts, it was shown that spermatozoa deliver their RNA payload to the oocyte at fertilization. These findings support the view that spermatozoa play a greater role in orchestrating fertilization and early embryonic development than previously thought. It is anticipated that these observations will have profound affects on the diagnosis and treatment of idiopathic male infertility. In addition, if paternal RNAs are indeed requisite for normal embryo development, their addition to recipient oocytes may enhance the success rate of somatic cell nuclear transfers as well as.
Additional microarray/bioinformatics resources available
Complementary DNAs (cDNAs), representing the RNA isolated from human testes and both pooled and individual ejaculate spermatozoal samples, were hybridized to a series of microarrays. The presence of a signal above the threshold is represented by a dot. Each signal was also then manually verified. Each numbered panel identifies the specific Gene Filter (Research Genetics). Those expressed sequence tags (ESTs) hybridized by testes cDNAs (T) are shown in red, those hybridized by the pooled-ejaculate cDNAs (P) are shown in green, while those hybridized by the individual-ejaculate cDNAs (I) are shown in blue.
When the T, P or I filter overlap, specific colors are generated as shown by the color-keys at the bottom of each image. The white boxes show the four ESTs that hybridized to the individual but not the pooled ejaculate cDNAs. These regions are enlarged and labeled by their corresponding Gene Filter in the bottom right corner. The upper (u) and lower (l) boxes on Gene Filter 203 are indicated.
The Lancet. 360:772-777
Ostermeier, G.C.,m Millmer, D., Huntriss, J.D., Diamond, M.P and Krawetz, S.A. (2004) Delivering spermatozoan RNA to the oocyte. Nature 429: 154. [PubMed]
Moldenhauer, J.S., Ostermeier, G.C., Johnson, A., Diamond, M.P. and Krawetz, S.A. (2003) Diagnosing Male Factor Infertility Using Microarrays. Journal of Andrology 24:783-789. [PubMed]
Ostermeier, G.C., Dix, D.J., Miller, D., Khatri, P., Krawetz, S.A. (2002) Spermatozoal RNA profiles of normal fertile men. The Lancet. 360:772-777. [PubMed] additional resources
van Biljon, W., Wykes, M., Scherer, S., Krawetz, S.A. and Hapgood J. (2002) Type II gonadotropin-releasing hormone-receptor transcripts in human sperm. Biology of Reproduction.67: 1741-1749. [PubMed]
Rockett, J.C., Luft, J.C., Garges, J.B., Krawetz, S.A., Hughes, M.R., Kim, K.W., Oudes, A.J. and Dix, D.J. (2001) Development of a 950-gene DNA array for examining gene expression patterns in mouse testis. Genome Biology 2:14.1-14.9. [PubMed]
Wykes, S. M., Miller, D. and Krawetz, S.A. (2000) Mammalian spermatozoal mRNAs: tools for functional analysis of male gametes.Journal of Submicroscopic Cytology and Pathology 32:77-81. [PubMed]
Miller, D., Briggs, S., Snowden, H., Hamlington, J., Rollision, S., Lilford, R. and Krawetz, S.A. (1999) A complex population of RNAs in human ejaculate spermatozoa: implications for understanding molecular aspects of spermiogenesis. Gene 237:385-392. [PubMed]
Wykes, S.M., Visscher, D.M. and Krawetz, S.A. (1997) Haploid expressed transcripts persist in mature human spermatozoa. Molecular Human Reproduction 3:15-19. [PubMed]