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

JCI Insight
Sungsam GongGordon Cs Smith

Abstract

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 t...Continue Reading

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Citations

Feb 16, 2019·The Journal of Clinical Endocrinology and Metabolism·Nimesh A JayasuriyaGordon C S Smith
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Datasets Mentioned

BETA
EGAD00001003136
EGAD00001003457

Methods Mentioned

BETA
RNA-seq
biopsies
DNA-seq
Methyl-Seq
PCR
methylation sequencing
cesarean section
metabolomic profiling

Software Mentioned

ENSEMBL
DESeq2 Bioconductor
SAMtools
Image J
FastQC
Trim Galore !
TopHat2
Bis
Stata
Bowtie2

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