Eggs and sperm take different developmental paths to get the same job done, suggests John Eppig of The Jackson Laboratory

Date: Oct. 24, 2012
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Bar Harbor, Maine—You don't need a scientist to tell you there are differences between males and females. But according to Jackson Laboratory Professor John Eppig, males and females use different sets of molecules to achieve some of the same crucial processes—meiosis and protection of DNA integrity—in the development of sperm and eggs.

John Eppig, Ph.D.In the Oct. 25 edition of the Proceedings of the National Academy of Sciences, Eppig proposes that MARF1, a protein expressed in oocytes, the cells that become eggs, does the work of a whole cluster or "nuage" of proteins in spermatocytes during the processes of meiosis and genome integrity.

Meiosis occurs during the development of spermatocytes and oocytes and reduces the number of chromosomes to half that found in other cells of the body, in preparation for fertilization. During meiosis, egg and sperm cells also must control retrotransposons, small "jumping genes" that can move around in the genome and endanger genomic integrity.

In the developing spermatocyte, these processes are managed by a complex of proteins—PIWI, PIWI-associated proteins and tudor proteins. "These proteins cluster together in a weird structure called ‘nuage' surrounding some of the cytoplasmic mitochondria," Eppig says.

Other groups have shown that when PIWI and PIWI-associated genes, as well as some tudor genes, are knocked out, two things happen in spermatogenesis: meiosis fails and retrotransposons go wild. That means the males are infertile, and nuage just disappears—"it goes poof!" says Eppig.

In oocytes, on the other hand, when those PIWI and PIWI-associated genes are knocked out, nothing happens. "The proteins encoded by these genes are not essential for female fertility," Eppig says. "The females of those knockouts are completely fertile. And also, in oocytes there's nothing that looks like nuage, but still we know that meiosis and control of retrotransposons go on."

Eppig and his colleagues showed that the protein MARF1 is crucial for oocyte development. In March Eppig's lab showed that mutations in a gene they named Marf1 in mice result in the arrest of meiosis during egg, but not sperm, development.

"Our hypothesis in this new paper," Eppig says, "is that MARF1 performs nuage-like functions in the female. This one protein appears to be able to carry out the processes that require several proteins in the male."

Eppig was inducted into the National Academy of Sciences last year; one of the privileges associated with that honor is presenting new hypotheses in an "inaugural" paper in the Academy's journal.

He muses, "Why did these separate processes for similar mechanisms and objectives in oocytes and spermatocytes evolve? I think that's really a mystery and something that needs more research."

The Jackson Laboratory is an independent, nonprofit biomedical research institution based in Bar Harbor, Maine, with a facility in Sacramento, Calif., and a new genomic medicine institute in Farmington, Conn. It employs a total staff of more than 1,400. Its mission is to discover the genetic basis for preventing, treating and curing human disease and to enable research and education for the global biomedical community.

Su et al.: MARF1 has nuage-like function in mammalian oocytes. Proceedings of the National Academy of Sciences, Online Early Edition, doi/10.1073/pnas.1216904109

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Joyce Peterson, 207-288-6058, The Jackson Laboratory

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