In murine placentas, peroxisome proliferator-activated receptor (PPAR)γ1, a nuclear receptor, is abundant at the late stage of pregnancy (E15−E16), but its functional roles are still elusive because PPARγ-full knockout embryos die early (E10). We generated mice disrupted in only Pparγ1, one of the two major mRNA splicing variants of PPARγ1. Pparγ1-knockout embryos developed normally until 15.5 dpc, but their growth was retarded thereafter and they did not survive. At 15.5 dpc, in the wild-type placentas, intense PPARγ-immunostaining was detected in sinusoidal trophoblast giant cells (sTGCs), a cell lineage that coordinates the maternal blood microcirculation in the labyrinth, whereas they were absent in the knockouts. Although Pparγ1-knockout placentas were normal in morphology, we observed severely dilated maternal blood sinuses in the labyrinth. The Pparγ1-knockout sTGCs had abnormally large nuclei, an enhanced endocycling phenotype, indicating insufficient differentiation. RNA-sequencing of the placentas showed increased expression of genes coding for nucleosome assembly factors. Labyrinthine gene expressions for atypical E2Fs and cyclin E, key drivers for endocycling, were increased >3-fold. These findings suggested that PPARγ1 plays a key role in endocycle termination.

中文翻译：

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Pparγ1的靶向破坏促进小鼠胎盘中滋养层的内复制

在鼠胎盘中，过氧化物酶体增殖物激活受体（PPAR）γ1（一种核受体）在妊娠晚期（E15-E16）丰富，但其功能性作用仍然难以捉摸，因为充满PPARγ的基因敲除胚胎较早死亡（E10） 。我们生成的小鼠仅在Pparγ1（PPARγ1的两个主要mRNA剪接变体之一）中受到破坏。Pparγ1敲除胚胎正常发育直至15.5 dpc，但此后其生长受阻，无法存活。在15.5 dpc时，在野生型胎盘中，在正弦形滋养层巨细胞（sTGCs）中检测到强烈的PPARγ免疫染色，该细胞谱系协调迷宫中母体血液的微循环，而在敲除物中则不存在。虽然Pparγ1-敲除胎盘在形态上是正常的，我们在迷宫中观察到母体血窦严重扩张。的PPARγ1敲除sTGCs具有异常大的细胞核，增强endocycling表型，表明分化不充分。胎盘的RNA测序显示编码核小体装配因子的基因表达增加。非典型E2F和细胞周期蛋白E（作为内循环的关键驱动力）的迷宫素基因表达增加了3倍以上。这些发现表明，PPARγ1在终止内循环中起关键作用。