Gestational diabetes mellitus (GDM) is associated with an increased risk of adverse pregnancy outcomes. Increasing evidence shows that placentation defects may play important roles in GDM. However, our understanding of the human placenta remains limited. In this study, we generated a comprehensive transcriptomic profile of cellular signatures and transcriptomes in the human placenta in GDM using single-cell RNA sequencing (scRNA-seq), constructed a comprehensive cell atlas, and identified cell subtypes and subtype-specific marker genes. In addition, we investigated the placental cellular function and intercellular interactions in GDM. These findings help to elucidate the molecular mechanisms of GDM, and may facilitate the development of new approaches to GDM treatment and prevention.

Wenbo Zhou, Huiyan Wang, Yuqi Yang, Fang Guo, Bin Yu, and Zhaoliang Su. Mol. Cells 2022;45:317-28. https://doi.org/10.14348/molcells.2021.0211

Objective: To explore the feasibility of high-throughput massively parallel genomic DNA sequencing technology for the noninvasive prenatal detection of fetal sex chromosome aneuploidies (SCAs). Methods: The study enrolled pregnant women who were prepared to undergo noninvasive prenatal testing (NIPT) in the second trimester. Cell-free fetal DNA (cffDNA) was extracted from the mother’s peripheral venous blood and a high-throughput sequencing procedure was undertaken. Patients identified as having pregnancies associated with SCAs were offered prenatal fetal chromosomal karyotyping. Results: The study enrolled 10 275 pregnant women who were prepared to undergo NIPT. Of these, 57 pregnant women (0.55%) showed fetal SCA, including 27 with Turner syndrome (45,X), eight with Triple X syndrome (47,XXX), 12 with Klinefelter syndrome (47,XXY) and three with 47,XYY. Thirty-three pregnant women agreed to undergo fetal karyotyping and 18 had results consistent with NIPT, while 15 patients received a normal karyotype result. The overall positive predictive value of NIPT for detecting SCAs was 54.54% (18/33) and for detecting Turner syndrome (45,X) was 29.41% (5/17). Conclusion: NIPT can be used to identify fetal SCAs by analysing cffDNA using massively parallel genomic sequencing, although the accuracy needs to be improved particularly for Turner syndrome (45,X).

This study explored the effectiveness of expanding newborn screening (NBS) by tandem mass spectrometry (TMS) and gene diagnosis by next-generation sequencing (NGS). First, we described the characteristics of gene variants in Jiangsu Province. We collected clinical data from three NBS centers. All infants followed a unified screening and diagnosis process. After obtaining informed consent, dried blood spots (DBSs) were collected and analyzed by TMS. If the results fell outside of the cut-off value, repeat analysis was performed. If the re-test results remained abnormal, the infant was recalled for further assessment. We performed targeted sequencing using the extended edition panel of inborn errors of metabolism (IEM) to detect 306 genes using the Illumina HiSeq 2500 platform. A total of 536,008 babies underwent NBS by TMS in three NBS centres. In total, 194 cases were eventually diagnosed with various types of inherited metabolic diseases, with an overall incidence of 1/2763. There were 23 types of diseases, including ten amino acid disorders (43.5%), eight organic acidaemias (34.8%) and five fatty acid oxidation defects (21.7%). In these infants, we clearly identified variants of disease-causing genes by next-generation sequencing (NGS). Most had two variants and others had one or three variants: 88% of gene variants were heterozygous and 12% were homozygous. There is a certain incidence of IEM in Jiangsu Province and it is necessary to carry out screening for 27 diseases. Meanwhile, NGS combined with TMS offers an enhanced plan for NBS for IEM.

Several biomarkers are used to measure iron deficiency (ID) during pregnancy, but the prevalence of ID and its association with adverse birth outcomes shows inconsistent results. The aim of this study was to examine the prevalence of ID in third trimester using multiple indicators of iron status and the relationship with birth outcomes in Chinese population. We conducted a retrospective observational cohort study of 11,581 pregnant women between 2016 and 2017 in Changzhou City, Jiangsu Province, China. We obtained the data (maternal characteristics and birth outcomes) and the concentrations of ID biomarkers from our hospitalization information system and laboratory information system, respectively. Using serum ferritin (SF), serum transferrin (ST) and their ratio as criteria of ID, we investigated associations between birth outcomes and late pregnancy ID. The prevalence of ID in our study was 51.82% as defined by low SF (< 12 μg/L), 54.43% as defined by high ST (> 4 g/L) and 53.90% as defined by high ratio of ST/SF (Log 10 transform > 5.52). Maternal ST/SF ratio was associated with higher mean birth weight (97.04 g; 95% CI, 74.28, 119.81 for the highest vs. lowest quartile). Third trimester maternal ID, defined by ST/SF ratio, was associated with lower risks of preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA) infants, higher risks of macrosomia and large for gestational age (LGA) babies (for PTB: OR = 0.53, 95% CI, 0.36–0.77; for LBW: OR = 0.44, 95% CI, 0.31–0.62; for SGA: OR = 0.69, 95% CI, 0.57–0.83; for macrosomia: OR = 1.39, 95% CI, 1.13–1.70; for LGA: OR = 1.20, 95% CI, 1.04–1.39). ID in the third-trimester of pregnancy are frequent in Chinese women. Our findings suggest that the ratio of ST/SF measured in late pregnancy could be useful as a significant predictor of unfavorable birth outcomes.

Preeclampsia (PE) is the main cause of maternal death in primipara, and commonly results in severe maternal and neonatal complications such as multiple organ dysfunction syndrome. However, the exact pathogenesis of this disease remains unclear. Circular RNAs (circRNAs) are noncoding RNAs that have been shown to be extensively involved in numerous physiological processes, but there is limited knowledge of their functions and mechanisms in PE. In the present study, we found the expression of a circRNA, hsa_circ_0088227 (circRNA of pregnancy-associated plasma protein A, circPAPPA), was down-regulated in both placenta and plasma samples from subjects with PE. Knockdown of circPAPPA led to decreased proliferation and invasion in HTR8-S/Vneo trophoblast cells. miR-384 was identified as a direct target of circPAPPA, and the gene encoding signal transducer and activator of transcription 3 (STAT3) was targeted by miR-384. We found that miR-384 was unregulated in PE, and overexpression of miR-384 could inhibit cell proliferation and invasion. In addition, we showed that the expression of STAT3 was decreased with knockdown of circPAPPA or the overexpression of miR-384 in trophoblast cells, but this decrease was partially reversed when co-transfection was performed with mimics of miR-384 inhibitor and si-circPAPPA. Together, these results suggest that down-regulation of circPAPPA facilitates the onset and development of PE by suppressing trophoblast cells, with involvement of the miR-384/STAT3 signaling pathway. Our study significantly increases the understanding of the occurrence and development of PE, and also provides a molecular target for the treatment of this disorder.