The role of the Dicer. MicroRNAs are emerging as major transcriptional and post-transcriptional regulators of gene expression. DICER, an RNaseIII enzyme, plays a role in the biogenesis of microRNAs; recently there has been a flurry of activity to determine the developmental role of DICER by whole-organism and conditional gene disruptions. In a paper on p. 696 of this issue, Maatouk et al. add important new information to the emerging story by demonstrating that DICER1 is required for normal spermatogenesis in the mouse. These authors used a conditional knockout (CKO) approach to delete Dicer1 in the germline. Because the CKO mice exhibited transient fertility, an elegant reporter strategy was used to demonstrate that elongated spermatids present in the CKO testes did express the Cre recombinase; therefore, it is likely that differentiation to this stage can occur in the absence of DICER1. Nonetheless, Dicer1 CKO spermatogenic cells exhibited disruption of microRNA processing and both quantitative and qualitative defects leading to the formation of functionally abnormal sperm. These data, together with other recent publications, suggest complex roles for microRNAs and their processing enzymes in both male and female germ cells and promise much interesting work to come.
Danielle M. Maatouk, Kate L. Loveland, Michael T. McManus, Karen Moore, and Brian D. Harfe. Dicer1 Is Required for Differentiation of the Mouse Male Germline. Biol Reprod 2008; 79:696-703. Published online in BOR-Papers In Press 16 July 2008; DOI 10.1095/biolreprod.108.067827
Perils of culture. There is growing interest in the developmental origins of adult disease, and effects of both nutrition and environment on oocytes and embryos on adult health of offspring have been demonstrated. However, mechanisms by which deleterious effects are established during these early developmental stages are unknown, although epigenetic processes have been suspected. Morgan et al. elegantly bolster the epigenetic hypothesis in a paper on p. 618 of this issue. The authors used a mouse "reporter" model for changes in methylation: the IAP (intracisternal A-particle) element that controls expression at the coat-color Avy (agouti viable yellow) allele; mice bearing this allele exhibit coat-color differences reflective of the extent of methylation on the IAP element. Morgan et al. found highly significant differences in color coats among offspring derived from either in vivo or in vitro preimplantation development, demonstrating that conditions for preimplantation development affected epigenetic regulation of the Avy locus. Thus, culture conditions used in this study did not mimic the normal (in vivo) environment for preimplantation development and this difference resulted in a clear effect on the adult phenotype. The Avy model will facilitate optimization of preimplantation culture of mouse embryos, and lessons learned from this approach in turn should be valuable for optimizing human preimplantation culture environments.
Hugh D. Morgan, Xing L. Jin, Aiqing Li, Emma Whitelaw, and Chris O'Neill. The Culture of Zygotes to the Blastocyst Stage Changes the Postnatal Expression of an Epigentically Labile Allele, Agouti Viable Yellow, in Mice. Biol Reprod 2008; 79: 618-623. Published online in BOR-Papers In Press 18 June 2008; DOI 10.1095/biolreprod.108.068213
Journal
Biology of Reproduction