Differentially expressed circular RNAs in maternal and neonatal umbilical cord plasma from SGA compared with AGA.

Small for gestational age (SGA) has a high risk of mortality and morbidity and is common in obstetrics. To date, no effective prediction and treatment tools are available. Acting as microRNA (miRNA) sponges and disease biomarkers are clear functions of circular RNAs (circRNAs). However, it is still unknown what role circRNAs act in SGA. To explore the role of circRNAs in SGA, circRNA expression patterns of the umbilical cord and maternal plasma in SGA was assessed. We first evaluated circRNAs in umbilical cord blood of the SGA and appropriate for gestational age (AGA) groups by microarray sequencing. In total, 170 340 circRNAs were sequenced, and 144 circRNAs were significantly upregulated while 977 were markedly downregulated. Has_circRNA15994-13, has_circ_0001359, and has_circ_0001360 were abundant and differentially expressed between the SGA and AGA groups, and confirmed in the umbilical cord and maternal blood specimens by reverse transcription polymerase chain reaction. By combining miRNA microarray data of the SGA placenta tissue in NCBI, it was found that two miRNAs were both hsa_circRNA15994-13 targets and differentially expressed, including hsa-miR-3619-5p and hsa-miR-4741. Further KEEG analysis revealed that the most significant pathway enriched by hsa-miR-3619-5p was Wnt signaling that is closely related to SGA; meanwhile, previous reports demonstrated that hsa-miR-3619-5p directly binds to ß-catenin to accommodate the Wnt/ß-catenin pathway, whereby the suggestive hsa_circRNA15994-13 → hsa-miR-3619-5p → ß-catenin signaling pathway may play an important part in SGA.

Oocyte-expressed yes-associated protein is a key activator of the early zygotic genome in mouse.

In early mammalian embryos, the genome is transcriptionally quiescent until the zygotic genome activation (ZGA) which occurs 2-3 days after fertilization. Despite a long-standing effort, maternal transcription factors regulating this crucial developmental event remain largely elusive. Here, using maternal and paternal mouse models of Yap1 deletion, we show that maternally accumulated yes-associated protein (YAP) in oocyte is essential for ZGA. Maternal Yap1-knockout embryos exhibit a prolonged two-cell stage and develop into the four-cell stage at a much slower pace than the wild-type controls. Transcriptome analyses identify YAP target genes in early blastomeres; two of which, Rpl13 and Rrm2, are required to mediate maternal YAP's effect in conferring developmental competence on preimplantation embryos. Furthermore, the physiological YAP activator, lysophosphatidic acid, can substantially improve early development of wild-type, but not maternal Yap1-knockout embryos in both oviduct and culture. These observations provide insights into the mechanisms of ZGA, and suggest potentials of YAP activators in improving the developmental competence of cultured embryos in assisted human reproduction and animal biotechnology.