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Developmental biology - The Placenta

Baby's Sex Affects Pregnancy Complications

Gene profiles of male and female placentas are very different...


The sex of a baby appears to control the level of small molecules known as metabolites that are found in a pregnant mother's blood. These metabolites can explain why risks of some diseases in pregnancy vary depending on whether the fetus is a boy or a girl.

This new research from the University of Cambridge is published in JCI Insight, and helps explain why, while still in-utero, male babies can reflect poor growth and girl babies can induce an increased risk for severe pre-eclampsia in the mother.

A team led by researchers at the Department of Obstetrics and Gynaecology, National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre in the UK, conducted detailed studies of more than 4,000 first time mothers, analysing samples of all placental and maternal blood. They found that the genetic profile of the placentas of male and female babies were very different. Many of the placental genes that differed according to the sex of the baby, had not previously been seen to differ by sex in other tissues of the body.

The team found that one of these uniquely sex-related placental genes controlled the level of a small molecule called spermine. Spermine is a metabolite - a substance involved in metabolism - and plays an important role in all cells and is even essential for the growth of some bacteria. Female placentas had much higher levels of the enzyme that makes spermine.
Mothers pregnant with girls had higher blood levels of a form of spermine compared to mothers pregnant with boys.

Placental cells from boy births were more susceptible to a drug that blocks spermine production. This is direct evidence for sex-related differences in placental metabolism of spermine.

Researchers also found the amount of spermine found in mothers pregnant with a girl predicted risk for pregnancy complications in this order:

High Levels are associated with an increased risk of pre-eclampsia (mother develops high blood pressure and kidney disease)

Low Levels are associated with an increased risk of poor fetal growth.

The patterns observed were all consistent with previous work which has shown that boys may be more vulnerable to the effects of fetal growth restriction and that being pregnant with a girl may lead to an increased risk of severe preeclampsia.
"In pregnancy and childbirth, the sex of the baby is at the forefront of many parents' minds, we do not even think of the placenta as having a sex.

"This work shows the placenta differs profoundly according to sex. These differences alter elements of the mother's blood and may even modify her risk for pregnancy complications.

"Understanding these differences could lead to predictive tests that could possibly reduce poor pregnancy outcomes."


Gordon Smith PhD, Professor, University of Cambridge, UK and study leader.

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 this is the first evidence to implicate polyamine metabolism in sex-related differences in placentally related complications of human pregnancy.

Authors
Sungsam Gong, Ulla Sovio, Irving L.M.H. Aye, Francesca Gaccioli, Justyna Dopierala, Michelle D. Johnson, Angela M. Wood, Emma Cook, Benjamin J. Jenkins, Albert Koulman, Robert A. Casero Jr., Miguel Constância, D. Stephen Charnock-Jones and Gordon C.S. Smith


Acknowledgements
The work was supported by NIHR Cambridge Biomedical Research Centre and the Medical Council.>

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Jul 23, 2018   Fetal Timeline   Maternal Timeline   News   News Archive




The genetic profile of the placentas of male and female babies are very different, and affect the
mother and their own grwoth differently. Image: Gordon Smith, University of Cambridge, UK


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