The human placenta mediates gaseous, fluid, and nutritional exchanges between the mother and the developing fetus, and its proper function determines both the outcome of pregnancy and the long-term health of the child. Placentation begins with implantation of the blastocyst into the endometrium: its outer layer, the trophoblast, subsequently differentiates into several cellular subtypes that form and renew placental tissues throughout pregnancy. Nevertheless, how placental gene expression evolves at the genome-wide scale, from the earliest gestational stages through to term, remains poorly understood. Obtaining a comprehensive view of normal placental development is an essential prerequisite for understanding the structural and functional abnormalities associated with pregnancy disorders, such as pre-eclampsia, which is linked to defective remodeling of the uterine spiral arteries.
To characterize these dynamics, the authors collected and integrated gene expression profiles of human placentas spanning a broad time window, from the 4th to the 40th week of gestation, derived from publicly available microarray datasets. Several bioinformatic approaches were combined: simple linear regression, weighted gene correlation network analysis (WGCNA) to cluster genes into co-expressed modules, followed by Gene Ontology and KEGG pathway enrichment analyses performed with the clusterProfiler tool. Temporal changes in the expression of individual genes were represented as curves after data scaling and fitting.
This strategy enabled the identification of a total of 5,173 genes involved at different periods of placentation. Annotation of these genes highlighted the relevant biological processes and signaling pathways, among which the authors chose to further investigate the PPAR (peroxisome proliferator-activated receptor) signaling pathway. Numerous genes related to lipid storage and metabolism showed marked variations over the course of gestation, notably members of the FABP family and the LPL gene. These observations were confirmed by lipid staining of placental sections (Oil Red O staining), which revealed a significant decrease in lipid droplet content between early in the first trimester and term.
This work provides a detailed description of the dynamics of biological processes and signaling pathways during human placentation. It offers new avenues for deciphering the normal functions of the placenta and how dysregulation of these pathways might be linked to pregnancy disorders. As an example, the results show that the PPAR pathway underlies a steady decline in placental lipid content over the course of pregnancy.