Celiac disease and pregnancy outcome: anti-transglutaminase antibodies effects on placental and endometrial functions

Abstract

Within the human placenta, the villous trophoblast takes over the part of separating fetal tissues from maternal blood. This villous epithelium is a unique tissue since its outermost layer is not composed of single cells but rather is a multinucleated layer without lateral cell borders, the syncytiotrophoblast. This syncytial layer has some features that make it unique in the human body: (1) It is the only syncytial epithelium in the human and the absence of any lateral cell borders hinders the passage of any cells, bacteria or viruses from mother to fetus. (2) It is a fetal tissue that comes into direct contact with a genetically different tissue, maternal blood. Hence, there is the need for this layer to develop strategies to remain immunologically undetected throughout pregnancy. (3) Although controversially discussed during the last fifty years, there seems to be a downregulation of transcriptional activity in the nuclei of the syncytiotrophoblast. The freshly fused nuclei still show transcriptional activity while staying within this syncytial layer, nuclei more and more lose this feature. This feature is not specific for the syncytiotrophoblast but can be found in other end-differentiated cells and tissues as well. The reasons why the syncytiotrophoblast should reduce the activity of its own nuclei and only depend on the material (organelles, proteins and RNA) introduced by fusion with cytotrophoblasts remain obscure. The specific features of the syncytiotrophoblast listed above are needed to integrate this unique tissue into placental barrier at the interface betweenmother and fetus. If there is defective integrating of this layer due to dysregulated transcriptional, epigenetic or physiological pathways, this may lead to pregnancy pathologies such as IUGR and preeclampsia or even spontaneous abortion.