Germ cells divide and differentiate in a unique local microenvironment under the control of somatic cells. Signals released in this niche instruct oocyte reentry into the meiotic cell cycle. Once initiated, the progression through meiosis and the associated program of maternal mRNA translation are thought to be cell-autonomous. Here we show that translation of a subset of maternal mRNAs critical for embryo development is under the control of somatic cell inputs. Translation of specific maternal transcripts increases in oocytes cultured in association with somatic cells and is sensitive to EGF-like growth factors that act only on the somatic compartment. In mice deficient in amphiregulin, decreased fecundity and oocyte developmental competence is associated with defective translation of a subset of maternal mRNAs. These somatic cell signals that affect translation require activation of the PI3K/AKT/mTOR pathway. Thus, mRNA translation depends on somatic cell cues that are essential to reprogram the oocyte for embryo development.

In fertilized mouse eggs, de novo transcription of embryonic genes is first observed during the S phase of the one-cell stage. This transcription, however, is mostly limited to the male pronucleus and possibly uncoupled from translation, making the functional meaning obscure. We found that one-cell mouse embryos respond to the osmotic shock of in vitro isolation with migration of HSF1, the canonical stress activator of mammalian heat shock genes, to pronuclei and by transient transcription of the hsp70.1, but not hsp70.3 and hsp90, heat shock genes. Isolated growing dictyate oocytes also display a nuclear HSF1 localization, but, in contrast with embryos, they transcribe both hsp70.1 and hsp70.3 genes only after heat shock. Intranuclear injection of double-stranded oligodeoxyribonucleotides containing HSE, GAGA box or GC box consensus sequences, and antibodies raised to transcription factors HSF1, HSF2, Drosophila melanogaster GAGA factor, or Sp1 demonstrated that hsp70.1 transcription depends on HSF1 in both oocytes and embryos and that Sp1 is dispensable in oocytes and inhibitory in the embryos. Hsp70.1 thus represents the first endogenous gene so far identified to be physiologically activated and tightly regulated after fertilization in mammals.

The T-cell leukemia/lymphoma 1 (TCL1) gene is expressed during T-cell and B-cell development and involved in the pathogenesis of T-cell and B-cell leukemias/ lymphomas. It also plays a key regulatory role in the maintenance of the proliferation versus differentiation balance of embryonic stem (ES) cells. We previously characterized the expression of TCL1 during preimplantation embryo development, namely in the cells from which ES cells are derived, and found that it shuttles between blastomere cortical regions and the nucleus by a cell cycle-dependent fashion and to be required for early blastomere proliferation, but not the acquisition of first embryonal differentiation traits. TCL1 promotes cell proliferation by heterodimerization with AKT/PKB, a serine/threonine kinase having a central role in the signaling pathways controlling cell proliferation and survival. We have now analyzed TCL1/AKT interaction in the preimplantation mouse embryo and found that TCL1 is not relevant to AKT phosphorylation in one-cell and two-cell embryos. Therefore, early mouse embryos display a physiological dissociation between the TCL1 functions of AKT phosphorylation and phosphorylated AKT transfer to nucleus, pinpointing the latter function as the essential one for the AKT-mediated promotion of cell proliferation. We also provide evidence that TCL1 enters one-cell embryo pronuclei, while phosphorylated AKT does not, suggesting that TCL1 also plays an AKT independent role(s) at the beginning of embryo development