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Placental polyamine metabolism differs by fetal sex, fetal growth restriction, and preeclampsia.

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Gong, Sungsam 
Aye, Irving Lmh 
Gaccioli, Francesca  ORCID logo
Dopierala, Justyna 


Preeclampsia and fetal growth restriction (FGR) are major causes of the more than 5 million perinatal and infant deaths occurring globally each year, and both are associated with placental dysfunction. The risk of perinatal and infant death is greater in males, but the mechanisms are unclear. We studied data and biological samples from the Pregnancy Outcome Prediction (POP) study, a prospective cohort study that followed 4,212 women having first pregnancies from their dating ultrasound scan through delivery. We tested the hypothesis that fetal sex would be associated with altered placental function using multiomic and targeted analyses. We found that spermine synthase (SMS) escapes X-chromosome inactivation (XCI) in the placenta and is expressed at lower levels in male primary trophoblast cells, and male cells were more sensitive to polyamine depletion. The spermine metabolite N1,N12-diacetylspermine (DiAcSpm) was higher in the female placenta and in the serum of women pregnant with a female fetus. Higher maternal serum levels of DiAcSpm increased the risk of preeclampsia but decreased the risk of FGR. To our knowledge, DiAcSpm is the first maternal biomarker to demonstrate opposite associations with preeclampsia and FGR, and this is the first evidence to implicate polyamine metabolism in sex-related differences in placentally related complications of human pregnancy.



Expression profiling, Obstetrics/gynecology, Polyamines, Reproductive Biology, Cell Survival, Female, Fetal Development, Fetal Growth Retardation, Gene Expression Regulation, Genes, X-Linked, Gestational Age, Humans, Male, Placenta, Polyamines, Pre-Eclampsia, Pregnancy, Pregnancy Complications, Prospective Studies, Risk Assessment, Sequence Analysis, RNA, Sex Factors, Spermine, Spermine Synthase, Transcriptome, Trophoblasts, Ultrasonography, Prenatal, United Kingdom

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JCI Insight

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American Society for Clinical Investigation
Medical Research Council (G1100221)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Cambridge University Hospitals NHS Foundation Trust (CUH) (3819-1718-09)
Biotechnology and Biological Sciences Research Council (BB/I014594/1)
Medical Research Council (MR/L003120/1)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (MC_UU_12012/4)
British Heart Foundation (None)
Medical Research Council (MR/K021133/1)
MRC (MC_UU_00014/4)
Medical Research Council (MC_PC_12012)
Medical Research Council (G1100221/1)
The work was supported by NIHR Cambridge Comprehensive Biomedical Research Centre and the Medical Research Council (United Kingdom; G1100221 to GCSS and DSC-J and MRC_MC_UU_12012/4 to MC).