Successful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus. Disorders in this process are tightly associated with adverse pregnancy outcomes including recurrent miscarriage (RM). However, an in-depth understanding of the systematic and decidual immune environment in RM remains largely lacking. In this study, we utilized single-cell RNA-sequencing (scRNA-seq) to comparably analyze the cellular and molecular signatures of decidual and peripheral leukocytes in normal and unexplained RM pregnancies at the early stage of gestation. Integrative analysis identifies 22 distinct cell clusters in total, and a dramatic difference in leukocyte subsets and molecular properties in RM cases is revealed. Specifically, the cytotoxic properties of CD8 + effector T cells, nature killer (NK), and mucosal-associated invariant T (MAIT) cells in peripheral blood indicates apparently enhanced pro-inflammatory status, and the population proportions and ligand–receptor interactions of the decidual leukocyte subsets demonstrate preferential immune activation in RM patients. The molecular features, spatial distribution, and the developmental trajectories of five decidual NK (dNK) subsets have been elaborately illustrated. In RM patients, a dNK subset that supports embryonic growth is diminished in proportion, while the ratio of another dNK subset with cytotoxic and immune-active signature is significantly increased. Notably, a unique pro-inflammatory CD56 + CD16 + dNK subset substantially accumulates in RM decidua. These findings reveal a comprehensive cellular and molecular atlas of decidual and peripheral leukocytes in human early pregnancy and provide an in-depth insight into the immune pathogenesis for early pregnancy loss.

The influence of El Niño-Southern Oscillation (ENSO) on northern midlatitude ozone during the period January-March (JFM) is investigated using various observations and a chemistry-climate model. The analysis reveals that, during El Niño events, there are noticeable anomalously high total ozone column (TOC) values over the North Pacific, the southern United States, northeastern Africa, and East Asia but anomalously low values in central Europe and over the North Atlantic. La Niña events have almost the opposite effects on TOC anomalies. The longitudinal dependence of midlatitude ozone anomalies associated with ENSO events during the period JFM is found to be related to planetary waves. Planetary waves excited by tropical convection propagate into the middle latitudes and give rise to longwave trains (Pacific-North American pattern) and shortwave trains along the North African-Asian jet. These wave trains affect ozone in the upper troposphere and lower stratosphere (UTLS) by modulating the midlatitude tropopause height and cause TOC anomalies by changing the vertical distributions of ozone. In addition, synoptic-scale Rossby wave breaking increases on the poleward flanks of the enhanced westerly jet during El Niño events, leading to a stronger eddy-driven meridional circulation in the UTLS and hence causing TOC increases over the North Pacific, the southern United States, northeastern Africa, and East Asia and vice versa for La Niña events. It is also found that the contribution of changes in Brewer-Dobson circulation due to anomalous planetary wave dissipation in the stratosphere during ENSO events to TOC changes in the middle latitudes for the period JFM is small, not more than 1 Dobson unit (DU) per month.

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