Two major obstetric diseases, preeclampsia (PE), a pregnancy-induced endothelial dysfunction leading to hypertension and proteinuria, and intra-uterine growth-restriction (IUGR), a failure of the fetus to acquire its normal growth, are generally triggered by placental dysfunction. Many studies have evaluated gene expression deregulations in these diseases, but none has tackled systematically the role of alternative splicing. In the present study, we show that alternative splicing is an essential feature of placental diseases, affecting 1060 and 1409 genes in PE vs controls and IUGR vs controls, respectively, many of those involved in placental function. While in IUGR placentas, alternative splicing affects genes specifically related to pregnancy, in preeclamptic placentas, it impacts a mix of genes related to pregnancy and brain diseases. Also, alternative splicing variations can be detected at the individual level as sharp splicing differences between different placentas. We correlate these variations with genetic variants to define splicing Quantitative Trait Loci (sQTL) in the subset of the 48 genes the most strongly alternatively spliced in placental diseases. We show that alternative splicing is at least partly piloted by genetic variants located either in cis (52 QTL identified) or in trans (52 QTL identified). In particular, we found four chromosomal regions that impact the splicing of genes in the placenta. The present work provides a new vision of placental gene expression regulation that warrants further studies.

两种主要的产科疾病，即先兆子痫（PE）（一种妊娠引起的内皮功能障碍，导致高血压和蛋白尿）和宫内生长受限（IUGR）（胎儿无法正常生长），通常是由胎盘功能障碍引发的。许多研究评估了这些疾病中基因表达失调的情况，但没有一个研究系统地解决了选择性剪接的作用。在本研究中，我们表明选择性剪接是胎盘疾病的一个基本特征，分别影响 PE 与对照和 IUGR 与对照中的 1060 和 1409 个基因，其中许多与胎盘功能有关。在 IUGR 胎盘中，选择性剪接会影响与妊娠特别相关的基因，而在先兆子痫胎盘中，它会影响与妊娠和脑部疾病相关的多种基因。此外，选择性剪接变异可以在个体水平上检测为不同胎盘之间的明显剪接差异。我们将这些变异与遗传变异相关联，以定义胎盘疾病中选择性剪接最强的 48 个基因子集中的剪接数量性状位点 (sQTL)。我们表明，选择性剪接至少部分是由位于顺式（已鉴定出 52 个 QTL）或反式（已鉴定出 52 个 QTL）的遗传变异所引导。特别是，我们发现了四个影响胎盘基因剪接的染色体区域。目前的工作为胎盘基因表达调控提供了新的视角，值得进一步研究。