Circulating cell-free RNA in the blood provides a potential window into the health, phenotype, and developmental programs of a variety of human organs. We used high-throughput methods of RNA analysis such as microarrays and next-generation sequencing to characterize the global landscape circulating RNA in a cohort of human subjects. By focusing on genes whose expression is highly specific to certain tissues, we were able to identify the relative contributions of these tissues to circulating RNA and to monitor changes in tissue development and health. As one application of this approach, we performed a longitudinal study on pregnant women and analyzed their combined cell-free RNA transcriptomes across all three trimesters of pregnancy and after delivery. In addition to the analysis of mRNA, we observed and characterized noncoding species such as long noncoding RNA and circular RNA transcripts whose presence had not been previously observed in human plasma. We demonstrate that it is possible to track specific longitudinal phenotypic changes in both the mother and the fetus and that it is possible to directly measure transcripts from a variety of fetal tissues in the maternal blood sample. We also studied the role of neuron-specific transcripts in the blood of healthy adults and those suffering from the neurodegenerative disorder Alzheimer's disease and showed that disease specific neural transcripts are present at increased levels in the blood of affected individuals. Characterization of the cell-free transcriptome in its entirety may thus provide broad insights into human health and development without the need for invasive tissue sampling.

https://www.pnas.org/content/pnas/111/20/7361.full.pdf

Noninvasive in vivo monitoring of tissue-specific global gene expression in humans

Controversy surrounds reports describing the derivation of human trophoblast cells from placentas and embryonic stem cells (ESC), partly due to the difficulty in identifying markers that define cells as belonging to the trophoblast lineage. We have selected criteria that are characteristic of primary first-trimester trophoblast: a set of protein markers, HLA class I profile, methylation of ELF5, and expression of microRNAs (miRNAs) from the chromosome 19 miRNA cluster (C19MC). We tested these criteria on cells previously reported to show some phenotypic characteristics of trophoblast: bone morphogenetic protein (BMP)-treated human ESC and 2102Ep, an embryonal carcinoma cell line. Both cell types only show some, but not all, of the four trophoblast criteria. Thus, BMP-treated human ESC have not fully differentiated to trophoblast. Our study identifies a robust panel, including both protein and non-protein-coding markers that, in combination, can be used to reliably define cells as characteristic of early trophoblast.

https://www.cell.com/stem-cell-reports/pdf/S2213-6711(16)00023-0.pdf

What Is Trophoblast? A Combination of Criteria Define Human First-Trimester Trophoblast

Cellular roles of ADAM12 in health and disease

Preeclampsia and intrauterine growth restriction (IUGR) are major contributors to perinatal mortality and morbidity worldwide. Both are characterized by impaired trophoblastic invasion of the maternal spiral arteries and their conversion from narrow muscular vessels to wide non-muscular channels. Despite improvement in the understanding of the pathophysiology of these conditions, ability to accurately identify pregnant woman who will develop them is limited. This greatly impairs the development and testing of preventive interventions. While different measures of placental dysfunction have been associated with increased risk for adverse pregnancy outcomes, the ability of any single one to accurately predict these outcomes is poor. Developing predictive tests is further challenged by difficulty in the timing of the measurements, as both the structural and biochemical characteristics of the placenta change with increasing gestational age. The ideal screening test would accurately predict the development of adverse pregnancy outcomes early enough to provide a window for preventive interventions. Improvement in ultrasound technology provides potentially useful novel tools for evaluating placental structure, but measurements need to be standardized in order to be useful. Maternal serum analyte screening is a noninvasive test of placental biochemical function, but present serum marker alone is not sufficiently accurate to suggest its routine use in clinical practice. The use of first trimester biochemical markers in combination with uterine artery Doppler screening is promising as a potential screening tool. Prospective longitudinal studies using standardized methodology are necessary to further evaluate the choice of parameters and strategies of combination to achieve the best predictive models.

https://obgyn.onlinelibrary.wiley.com/doi/epdf/10.1002/pd.2475

First-trimester assessment of placenta function and the prediction of preeclampsia and intrauterine growth restriction

Metallo-aminopeptidase inhibitors

Adipocyte-derived leucine aminopeptidase (A-LAP) is a novel zinc-metallopeptidase involved in angiotensin II (AngII) metabolism, cell migration and antigen presentation. These functions are implicated

Expression of adipocyte-derived leucine aminopeptidase in endometrial cancer: Association with tumor grade and CA-125

Ultrastructural localization of aminopeptidase A/angiotensinase and placental leucine aminopeptidase/oxytocinase in chorionic villi of human placenta

ADAMs, a disintegrin and metalloproteinases, mediate shedding of oxytocinase

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Expression of adipocyte-derived leucine aminopeptidase in endometrial cancer: Association with tumor grade and CA-125

Ultrastructural localization of aminopeptidase A/angiotensinase and placental leucine aminopeptidase/oxytocinase in chorionic villi of human placenta

ADAMs, a disintegrin and metalloproteinases, mediate shedding of oxytocinase