Father's sperm packs more than just a fertilizer

The major function of a man's sperm was fertilization, scientists once thought. True, sperm contains the father's chromosomes; but new studies from Wayne State University show that RNAs critically important to early growth of an embryo are also delivered.

Early embryonic development--once considered "women's work" that was solely steered by the female egg--is actually a partnership with paternal RNA delivered by the sperm at the point of fertilization. In other words, in addition to rousing the egg, the male RNA also participates in oocyte activation, the transition from maternal to embryonic gene control and the establishment of imprints in early embryos. This major paradigm shift suggests that messenger RNAs (mRNAs) turn on a crucial development switch and deliver critical functioning mechanisms to the egg, report Wayne State University researchers in the May 13 issue of Nature.

Stephen Krawetz, Ph.D., a WSU professor and senior author on the paper, along with colleagues including David Miller from the University of Leeds, UK, and other WSU researchers, have already documented the presence of RNA strands in sperm. In 2002, they used genetic analysis to identify 3,000 individual mRNAs for the fertile male and have begun to identify defective genes that contribute to infertility and record exposure to environmental toxicants.

Their new work shows that the viability of the sperm goes beyond factors like motility and quantity required for fertilization. The healthy sperm contributes to the viability of the zygote even after fertilization. "Men have a greater role in early development than we previously thought," Dr. Krawetz said.

This expanded view of sperm's responsibility may also explain why cloning has turned out to be so difficult. "Cloning requires an egg to develop without sperm fertilization, and although an egg may be manipulated or 'tricked' in the laboratory some of the time, embryonic growth generally requires an activation signal that comes from the male sperm," Dr. Krawetz said.

He also notes the timeliness of this study given the April publication of Nature that featured Japanese and South Korean scientists who created a mouse born of all-female DNA. "In contrast, we show that men are not obsolete," Dr. Krawetz said. "Our understanding of these RNAs will certainly enhance our knowledge of the father's influence on early zygotic and embryonic development. Dad indeed has a function."

Stephen Krawetz is the Charlotte B. Failing Professor in Wayne State University's Department of Obstetrics and Gynecology, and is also professor in the Center for Molecular Medicine and Genetics, and Institute for Scientific Computing. Co-authors are: G. Charles Ostermeier (WSU), David Miller (University of Leeds), John Huntriss (Leeds) and Michael Diamond (WSU).

The full article titled "Delivering spermatozoan RNA to the oocyte" can be viewed online beginning May 13 at: www.nature.com

With more than 1,000 medical students, WSU is among the nation's largest medical schools. Together with its clinical partner, the Wayne State University Physician Group, the school is a leader in patient care and medical research in a number of areas, including cancer, genetics, neuroscience and women's and children's health.

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