CXCL5 Downregulation in Villous Tissue Is Correlated With Recurrent Spontaneous Abortion

Recurrent spontaneous abortion (RSA) affects 5% of childbearing-age women worldwide. Inadequate trophoblast invasion is one of the main reasons for the development of RSA; however, the underlying molecular mechanisms for RSA have not been fully understood, and further explanation is urgently needed. C-X-C motif chemokine ligand 5 (CXCL5) is reported to contribute to the invasion of cancer cells, and its aberrant expression is associated with the cellular process of tumor pathology. Considering the high behavioral similarity between trophoblast cells and cancer cells, we hypothesized that CXCL5 may influence trophoblast invasion, and its expression levels in villous tissue may be correlated with RSA. In this study, we firstly investigated the CXCL5 expression in placental villous tissues of 15 RSA patients and 13 control patients, and the results showed that CXCL5 levels were significantly lower in villous tissue from RSA patients than those of the controls. Further in vitro experiments presented that recombinant human CXCL5 can enhance trophoblast migration, invasion, and epithelial-to-mesenchymal transition (EMT) process. We also demonstrated that CXCL5 exerted these effects on trophoblast cells through PI3K/AKT/ERK1/2 signaling pathway. In conclusion, these data indicate that CXCL5 downregulation in human villous tissue is correlated with RSA. Additionally, we found that estrogen, progesterone, human chorionic gonadotropin, and decidual stromal cells can regulate CXCL5 and chemokine receptor 2 (CXCR2) expression of trophoblast in a cell manner.

Quantifying the impact of tissue metabolism on solute transport in feto-placental microvascular networks

The primary exchange units in the human placenta are terminal villi, in which fetal capillary networks are surrounded by a thin layer of villous tissue, separating fetal from maternal blood. To understand how the complex spatial structure of villi influences their function, we use an image-based theoretical model to study the effect of tissue metabolism on the transport of solutes from maternal blood into the fetal circulation. For solute that is taken up under first-order kinetics, we show that the transition between flow-limited and diffusion-limited transport depends on two new dimensionless parameters defined in terms of key geometric quantities, with strong solute uptake promoting flow-limited transport conditions. We present a simple algebraic approximation for solute uptake rate as a function of flow conditions, metabolic rate and villous geometry. For oxygen, accounting for nonlinear kinetics using physiological parameter values, our model predicts that villous metabolism does not significantly impact oxygen transfer to fetal blood, although the partitioning of fluxes between the villous tissue and the capillary network depends strongly on the flow regime.

Differential miRNA expression profiles between the first and third trimester human placentas

To determine placental microRNA (miRNA) expression at different gestational age, total RNA from six first and six third trimester placentas was isolated. miRNA expression was analyzed by Affymetrix miRNA microarray, and miRNA clusters were identified by web-based programs MirClust and miRGen Cluster. qRT-PCR was carried out to validate miRNA expression, and in situ hybridization (ISH) was performed to determine compartmental localization of miRNAs within villous tissue. A total of 208 miRNA transcripts, which represent 191 mature miRNAs, were found differently expressed between first and third trimester placentas. miRNAs within the miR-17-92 cluster, C14MC, miR-371 cluster, and C19MC were significantly upregulated in the first trimester placentas. In contrast, miRNAs of the let-7 family, miR-34 family, miR-29a cluster, miR-195 cluster, and miR-181c cluster were significantly upregulated in the third trimester placentas. Increased miR-371–5p, miR-17-3p, and miR-708–5p expression and decreased miR-125b-5p and miR-139–5p expression in the first trimester placentas were confirmed by qRT-PCR. Different expression pattern for miR-371-5p and miR-125b-5p within villous tissue was demonstrated by ISH. Distinct miRNA cluster expression profiles between the first and third trimester placentas were identified. miRNAs that regulate innate/adaptive immune responses are strongly expressed in both first and third trimester placentas. miRNAs that exert oncogenic, angiogenic, and antiapoptotic properties are dominantly expressed in the first trimester placentas, whereas miRNAs that promote cell differentiation and function as tumor suppressors are strongly expressed in the third trimester placentas. These results indicate that miRNAs play critical roles in placental development.