Systems Biology of Reproduction Lendulet Group, Institute of Enzymology, Research Centre for Natural Sciences, H-1117 Budapest, Hungary.
Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20692, and Detroit, MI 48201, USA.
Int J Mol Sci. 2020 Jan 17;21(2):628. doi: 10.3390/ijms21020628.
The human placenta maintains pregnancy and supports the developing fetus by providing nutrition, gas-waste exchange, hormonal regulation, and an immunological barrier from the maternal immune system. The villous syncytiotrophoblast carries most of these functions and provides the interface between the maternal and fetal circulatory systems. The syncytiotrophoblast is generated by the biochemical and morphological differentiation of underlying cytotrophoblast progenitor cells. The dysfunction of the villous trophoblast development is implicated in placenta-mediated pregnancy complications. Herein, we describe gene modules and clusters involved in the dynamic differentiation of villous cytotrophoblasts into the syncytiotrophoblast. During this process, the immune defense functions are first established, followed by structural and metabolic changes, and then by peptide hormone synthesis. We describe key transcription regulatory molecules that regulate gene modules involved in placental functions. Based on transcriptomic evidence, we infer how villous trophoblast differentiation and functions are dysregulated in preterm preeclampsia, a life-threatening placenta-mediated obstetrical syndrome for the mother and fetus. In the conclusion, we uncover the blueprint for villous trophoblast development and its impairment in preterm preeclampsia, which may aid in the future development of non-invasive biomarkers for placental functions and early identification of women at risk for preterm preeclampsia as well as other placenta-mediated pregnancy complications.
人类胎盘通过提供营养、气体-废物交换、激素调节以及来自母体免疫系统的免疫屏障来维持妊娠并支持胎儿发育。绒毛合体滋养层承担着大部分这些功能，并为母体和胎儿循环系统之间提供界面。合体滋养层是由底层细胞滋养层祖细胞的生化和形态分化产生的。绒毛滋养层功能障碍与胎盘介导的妊娠并发症有关。本文中，我们描述了参与绒毛细胞滋养层向合体滋养层动态分化的基因模块和簇。在此过程中，首先建立免疫防御功能，然后发生结构和代谢变化，随后进行肽激素合成。我们描述了调节参与胎盘功能的基因模块的关键转录调节分子。基于转录组证据，我们推断早产子痫前期（一种危及母亲和胎儿生命的胎盘介导的产科综合征）中绒毛滋养层分化和功能如何失调。在结论中，我们揭示了早产子痫前期中绒毛滋养层发育及其损伤的蓝图，这可能有助于未来开发用于胎盘功能的非侵入性生物标志物，并及早识别有早产子痫前期及其他胎盘介导的妊娠并发症风险的女性。
