Placental polyamine metabolism differs by fetal sex, fetal growth restriction, and preeclampsia.
Johnson, Michelle D
Jenkins, Benjamin J
Casero, Robert A
American Society for Clinical Investigation
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Gong, S., Sovio, U., Aye, I., Gaccioli, F., Dopierala, J., Johnson, M. D., Wood, A., et al. (2018). Placental polyamine metabolism differs by fetal sex, fetal growth restriction, and preeclampsia.. JCI Insight, 3 (13) https://doi.org/10.1172/jci.insight.120723
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.
Trophoblasts, Placenta, Humans, Pregnancy Complications, Fetal Growth Retardation, Pre-Eclampsia, Spermine, Polyamines, Spermine Synthase, Ultrasonography, Prenatal, Risk Assessment, Prospective Studies, Sequence Analysis, RNA, Sex Factors, Cell Survival, Gene Expression Regulation, Fetal Development, Gestational Age, Pregnancy, Female, Male, Genes, X-Linked, Transcriptome, United Kingdom
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).
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)
External DOI: https://doi.org/10.1172/jci.insight.120723
This record's URL: https://www.repository.cam.ac.uk/handle/1810/280456
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/