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Fetal sex differences play an important role in the pathophysiology of several placenta-related pregnancy complications. We previously reported that the maternal circulating level of a polyamine metabolite was altered in a fetal sex-specific manner, and was associated with pre-eclampsia and fetal growth restriction. Here we show that placental polyamine metabolism is altered in these disorders and that polyamines influence widespread changes in gene expression by regulating the availability of acetyl-CoA which is necessary for histone acetylation. Sex differences in polyamine metabolism are associated with escape from X chromosome inactivation of the gene encoding the enzyme spermine synthase in female placentas, as evidenced by biallelic expression of the gene in female trophoblasts. Polyamine depletion in primary human trophoblasts impairs glycolysis and mitochondrial metabolism resulting in decreased availability of acetyl-CoA and global histone hypoacetylation, in a sex-dependent manner. Chromatin-immunoprecipitation sequencing and RNA–sequencing identifies downregulation of progesterone biosynthetic pathways as a key target and polyamine depletion reduced progesterone release in male trophoblasts. Collectively, these findings suggest that polyamines regulate placental endocrine function through metabolic regulation of gene expression, and that sex differences in polyamine metabolism due to XCI escape may buffer the effects of placental dysfunction in pregnancy disorders.

See page 503 for the editorial comment on this article (doi:10.1093/eurheartj/ehi681)Aims Coronary dissections left untreated after percutaneous coronary intervention are associated withunfavourable outcomes. However, their role after drug-eluting stent (DES) implantation is still unde-scribed. We assessed incidence, predictors, and outcomes of residual dissections in DES-treated lesions.Methods and results Consecutive patients undergoing DES implantation were enrolled in four Italiancentres, with baseline, procedural, and outcome data entered into a dedicated database. Residual dis-sections were classified according to the National Heart Lung and Blood Institute criteria. End-pointsof interest were in-hospital, 1-month, and 6-month major adverse cardiovascular events (MACE, i.e.death, myocardial infarction, or target vessel revascularization), and stent thrombosis (ST). Amongthe 2418 included patients (4630 lesions), a total of 77 (1.7%) final dissections occurred in 67 (2.8%) sub-jects. Dissections were more frequent in longer and complex lesions and in the left anterior descending,and were associated with increased rates of in-hospital (11.9 vs. 5.2%, P ¼ 0.017) and 1-month MACE(13.4 vs. 6.0%, P ¼ 0.013), with similar 6-month trends. Cumulative ST was also greater in patientswith dissections (6.3 vs. 1.3%, P ¼ 0.011). Even non-obstructive dissections with thrombolysis in myocar-dial infarction 3 flow conferred a significantly worse prognosis.Conclusion This study, reporting for the first time on incidence, predictors, and outcomes of residualdissections in DES-treated coronary lesions, demonstrates their adverse clinical impact and supportsthe pursuit of a strategy of sealing dissection flaps with other DES.