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 >5 million perinatal and infant death 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 study (POPs), a prospective cohort study which followed 4,212 women having first pregnancies from their dating ultrasound scan through to delivery. We tested the hypothesis that fetal sex would be associated with altered placental function using multi-omic and targeted analyses. We found that spermine synthase (SMS) escapes-chromosome inactivation (XCI) in the placenta, is expressed at lower levels in male primary trophoblast cells and male cells were more sensitive to olyamine 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. 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 placentallyrelated 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).
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)
British Heart Foundation (RG/13/13/30194)
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/