Embryonic Rather than Extraembryonic Tissues Have More Impact on the Development of Placental Hyperplasia in Cloned Mice

Genetic-epigenetic intersection in trophoblast differentiation: Implications for extraembryonic tissue function

“…Reproduction Important insights into the origins of placental defects of NT conceptuses have also been gained from reciprocal complementation assays with tetraploid embryos. 56,57 In this constellation the tetraploid cell population contributes preferentially to the trophoblast compartment but is generally excluded from the embryo proper. 58 These experiments suggested that the later-onset placentomegaly phenotype may be a non-cell autonomous defect that originates mostly in the embryo proper thus pointing towards an altered signalling from the NT embryonic compartment to the extraembryonic tissues as the cause of placental overgrowth (Fig.…”

Functional full-term placentas formed from parthenogenetic embryos using serial nuclear transfer

“…We surmised that, even if the clonedparthenogenetic embryos had a lethal phenotype, the injected normal ES cells might support development to full term if supported by a normally functional placenta. In some cases, tetraploid cloned embryos (Miki et al, 2009) generated from pES cell nuclei were used to avoid the contribution of lethal parthenogenetic cells into foetuses. Surprisingly, when we examined G5 or G6 cloned-parthenogenetic chimeric embryo development at 19.5 d.p.c., we could obtain full-term offspring with large placentas (Table 3).…”

Trophoblast stem cells derived from nuclear transfer embryos: Phenotypically unique, bad neighbors, or poor communicators?

“…The latter is the consequence of being exposed to a defective niche, a view supported by tetraploid complementation experiments (9). Another recent report (6) confirms the ease of ntTS cell derivation but suggests that these cells may possess some unique features that could contribute to placentomegaly.…”

“…Insights into the etiology of nuclear transfer-associated placentomegaly have also been derived from tetraploid recombination experiments (8,9). These experiments are based on (i) the ability to produce one-cell tetraploid embryos from two-cell embryos by electrofusion, (ii) the competence of embryos generated by aggregating tetraploid and euploid embryonic cells to generate live offspring, and (iii) the developmental restriction of tetraploid embryonic cells within the newly formed chimeric embryos to extraembry- Fertilized embryos developing in vivo generate placentas with two well-defined compartments: junctional zone and labyrinth zone.…”

“…Aggregation of fertilized embryos with tetraploid nuclear transfer embryos results in normal placentation, whereas aggregation of nuclear transfer embryos with tetraploid-fertilized embryos yields placentomegaly (9). A caveat to these tetraploid recombination experiments concerns the unknown impact of the tetraploid genome on the trophoblast lineage.…”