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For some time, it has been proposed that there are competitive advantages to skewed sex ratio of litters, but mechanisms by which this occurs are poorly understood. It is known that there is skewing of sex ratio towards males among pups born to mice fed diets high in saturated fat. In a paper on p. 599 that is bound to stimulate discussion about the "whys" and "hows," Alexenko et al. demonstrate contrasting effects of ad libitum and restricted feeding of such diets. They hypothesized that male-biased litters, which occur when female mice are maintained continuously on high saturated fat diets, would also occur when the diet is restricted (but still sufficient for weight gain and fertility). Surprisingly, the results did not support this hypothesis; litters of restricted-diet females were not skewed toward males but instead toward daughters. The results prompt rethinking of assumptions and suggest that ease of access to calorie-rich food, and not body condition per se, favors male-biased sex ratios among progeny.
Andrei P. Alexenko, Jiude Mao, Mark R. Ellersieck, Angela M. Davis, Jeffrey J. Whyte, Cheryl S. Rosenfeld, and R. Michael Roberts. The Contrasting Effects of Ad Libitum and Restricted Feeding of a Diet Very High in Saturated Fats on Sex Ratio and Metabolic Hormones In Mice. Biol Reprod 77:599–604. Published online in BOR-Papers In Press 23 May 2007; DOI 10.1095/biolreprod.107.062174
Key to identifying those attributes that define stem cells is resolving what causes stem cells to differentiate. Genetic analysis had previously shown that the GDNF ligand-RET receptor pathway was important to the balance of spermatogonial stem cell renewal and differentiation. Now a paper on p. 723 studies GFRA1, a co-receptor of RET for GDNF, and reveals the expression patterns of GFRA1 that underlie this phenomenon. He et al. demonstrate that GFRA1 is expressed in a subpopulation of spermatogonia that also express POU5F1 (also known as OCT4), a marker for stem cells, and that spermatogonia expressing GFRA1 exhibit proliferation and colony-forming ability in culture. Grfa1 siRNAs knocked down expression of mRNA and GRFA1 protein and induced differentiation, notably elevated expression of KIT, decreased expression of POU5F1 and PCNA, and decreased RET phosphorylation. Thus, one component of the switch from renewal of spermatogonial stem cells to differentiation is elucidated, and this may lead to methods to maintain the stem cells in vitro.
Zuping He, Jiji Jiang, Marie-Claude Hofmann, and Martin Dym. Gfra1 Silencing in Mouse Spermatogonial Stem Cells Results in Their Differentiation via the Inactivation of RET Tyrosine Kinase. Biol Reprod 77:723–733. Published online in BOR-Papers In Press 11 July 2007; DOI 10.1095/biolreprod.107.062513
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