When provided with RNA precursors, mammalian spermatozoa synthesize RNA. Fractionation studies indicate sperm heads and midpiece-tails are both capable of RNA synthesis, two processes that can be readily distinguished by parameters of synthesis, effects of inhibitors, and by characterization of the different DNA-dependent RNA polymerases involved. It is proposed to define the physiological function(s) of the two classes of RNA synthesized in sperm with a series of "in vitro" fertilization experiments with mice. A comparison will be made of the numbers of blastocysts and progeny born to surrogate mothers in control and experimental animals in which RNA synthesis in sperm heads or sperm midpieces has been inhibited. Statistically significant decreases in progeny will demonstrate that the male gamete serves as more than simply a trigger at fertilization and that sperm RNA plays an essential role in development of the fertilized ovum. In addition, the biochemical properties of the paternal mitochondria and its role in embryonic development will be investigated to define the molecular basis for the phenomenon of maternal inheritance . Elucidation of the molecular events in sperm prior to and after fertilization that are necessary for successful fertilizations in mammals (mice) will provide criteria to ascertain normal interactions between sperm and egg. Such knowledge will help identify epigenetic and nuclear regulated processes that are essential for normal mammalian development. A better understanding of these events is necessary to explain how perturbations could lead to birth defects. In addition a more detailed comprehension of the biochemical events at fertilization will provide necessary information to aid in the treatment of the infertile and may provide superior approaches to fertility control.
NIH ExPorter
NIH ExPorter