First Author | Nakano T | Year | 2021 |
Journal | Dev Biol | Volume | 478 |
Pages | 222-235 | PubMed ID | 34246625 |
Mgi Jnum | J:311151 | Mgi Id | MGI:6764061 |
Doi | 10.1016/j.ydbio.2021.07.003 | Citation | Nakano T, et al. (2021) Effects of Ppargamma1 deletion on late-stage murine embryogenesis and cells that undergo endocycle. Dev Biol 478:222-235 |
abstractText | Peroxisome proliferator-activated receptor (PPAR) gamma1, a nuclear receptor, is abundant in the murine placenta during the late stage of pregnancy (E15-E16), although its functional roles remain unclear. PPARgamma1 is encoded by two splicing isoforms, namely Ppargamma1canonical and Ppargamma1sv, and its embryonic loss leads to early (E10) embryonic lethality. Thus, we generated knockout (KO) mice that carried only one of the isoforms to obtain a milder phenotype. Ppargamma1sv-KO mice were viable and fertile, whereas Ppargamma1canonical-KO mice failed to recover around the weaning age. Ppargamma1canonical-KO embryos developed normally up to 15.5 dpc, followed by growth delays after that. The junctional zone of Ppargamma1canonical-KO placentas severely infiltrated the labyrinth, and maternal blood sinuses were dilated. In the wild-type, PPARgamma1 was highly expressed in sinusoidal trophoblast giant cells (S-TGCs), peaking at 15.5 dpc. Ppargamma1canonical-KO abolished PPARgamma1 expression in S-TGCs. Notably, the S-TGCs had unusually enlarged nuclei and often occupied maternal vascular spaces, disturbing the organization of the fine labyrinth structure. Gene expression analyses of Ppargamma1canonical-KO placentas indicated enhanced S-phase cell cycle signatures. EdU-positive S-TGCs in Ppargamma1canonical-KO placentas were greater in number than those in wild-type placentas, suggesting that the cells continued to endoreplicate in the mutant placentas. These results indicate that PPARgamma1, a known cell cycle arrest mediator, is involved in the transition of TGCs undergoing endocycling to the terminal differentiation stage in the placentas. Therefore, PPARgamma1 deficiency, induced through genetic manipulation, leads to placental insufficiency. |