January issue of Biology of Reproduction - Highlights

The January 2005 issue of Biology of Reproduction marks the start of the co-editorship of Drs. John Eppig and Mary Ann
Handel. The new editors-in-chief, along with members of their board of associate editors, will provide highlights of some of
the prominent papers in each issue of the journal. Following are the January highlights of groundbreaking papers dealing with
genetic modification of germline stem cells and offering new insights into the "2-cell block" of embryo development in vitro.



"Genetic selection of mouse male germline stem cells in vitro: Offspring from single stem cells." Mito Kanatsu-Shinohara,
Shinya Toyokuni, and Takashi Shinohara.


Since the classic work of Brinster and colleagues demonstrating that spermatogonial stem cells could be transplanted within
seminiferous tubules, where they proliferate and undergo sperm development, it has been hoped that the system could be
adapted for germline modifications. This, however, entails a number of challenging technical steps such as the propagation of
cultures of spermatogonial stem cells, introduction of genetic modifications, and selection of the modified stem cells. Mito
Kanatsu-Shinohara and colleagues met the first challenge with a cocktail of growth factors, published previously in Biology
of Reproduction (Kanatsu-Shinohara M, Ogonuki N, Inoue K, Miki H, Ogura A, Toyokuni S, Shinohara T. Long-term proliferation
in culture and germline transmission of mouse male germline stem cells. Biol Reprod 2003; 69: 612-616.); they refer to the
spermatogonial stem cells established in this way as germline stem cells (GS). In the January 2005 issue of Biology of
Reproduction, this group reports another very significant step forward. They transfected the GS cells with a construct
designed to express both enhanced green fluorescent protein (EGFP) and neo to allow drug selection of modified cells. The
colonies derived from single modified and selected GS cells were expanded and then injected into seminiferous tubules of germ
cell-free mutant mice. After mating, these mice produced offspring that not only expressed the introduced EGFP construct but
also passed it on to their offspring and subsequent generations. This groundbreaking work sets the stage for further germline
modifications that will be important for a wide range of experimental analyses. Further, this work will have profound
implications if the technologies can be applied to the clinic. (The full text of this paper is available from Biology of
Reproduction--Papers in Press at biolreprod/cgi/rapidpdf/biolreprod.104.035659v1.pdf)


"Similar effects of osmolarity, glucose, and phosphate on cleavage past the 2-Cell stage in mouse embryos from outbred and F1
hybrid females." Timin Hadi, Mary-Anne Hammer, Carolyn Algire, Tiffany Richards, and Jay M. Baltz.


For many years it has been a puzzle why embryos from most random-bred and inbred female mice exhibit a block at the 2-cell
stage in classical embryo culture media. Because embryos of many F1 hybrids develop beyond this stage, it has been thought
that the phenotype is dependent on the genotype of the female giving rise to the egg - there are "blocking" and
"non-blocking" types of females. In the January 2005 issue of Biology of Reproduction, Hadi, Hammer, Algire, Richards, and
Baltz revisit this issue. The recent development of media in which even blocking embryos develop to the blastocyst stage
allowed them to address specific properties implicated in the 2-cell block and to test the hypothesis that the 2-cell block
is not restricted to particular genotypes, but that instead there is varying susceptibility. They show that both blocked and
non-blocked embryos are indeed susceptible to culture effects, with differences in the threshold of susceptibility. Increase
in osmolarity or glucose/phosphate levels can cause 2-cell arrest of both blocking and non-blocking embryos, and the blocking
effect of osmolarity is rescued by glycine. These results not only clear up long-standing confusion about the etiology of the
2-cell block but also highlight the important effects of culture conditions on experimental design. (The full text of this
paper is available from Biology of Reproduction--Papers in Press at biolreprod/cgi/rapidpdf/biolreprod.104.033324v1.pdf).


Biology of Reproduction, published by the Society for the Study of Reproduction, is the top-rated peer-reviewed journal in
the field of reproductive biology.


Contact: Dr. John Eppig

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207 288-6349

Society for the Study of Reproduction